Neoplasms, Gastrointestinal Tract
Conditions
Keywords
unresectable, HER2, ErbB2, TYKERB, capecitabine, CapeOx, gastric/esophageal cancer, GE junction, metastatic, lapatinib, oxaliplatin
Brief summary
This was an international multi-center trial that enrolled patients with locally advanced, unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose tumors had amplification of the ErbB2 (HER2) gene. The trial investigated whether lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx), extended the time to progression and overall survival. Tumor ErbB2 (HER2) status had to be known before trial entry. CapeOx was administered to all patients, and patients were randomly assigned to receive either lapatinib or placebo.
Interventions
DRUGLapatinib
5 pills at 250mg each once daily
DRUGPlacebo
5 pills once daily
DRUGCapecitabine
1700mg/m2/day in two daily doses
DRUGOxaliplatin
130mg/m2 on day 1
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: * Histologically confirmed gastric adenocarcinoma or adenocarcinoma of the esophagus or gastro-esophageal junction. * Gastric cancer that is unresectable due to locally advanced (defined as stage IV: T4N1-3 or TanyN3), metastatic, or locally recurrent disease; Esophageal cancer that is unresectable due to locally advanced (T3N1 or T4Nany), metastatic or locally recurrent disease. * Measurable or non-measurable, but radiologically evaluable disease, according to RECIST. * HER2 amplification by FISH assessed by the local or designated central laboratory; Subjects with unknown HER2 status were not eligible. * Adequate organ function, as defined in the study protocol, assessed within 14 days prior randomization. * Cardiac ejection fraction within institutional range of normal as measured by echocardiogram (ECHO). * Prior/Concurrent Therapy: * At least 3 weeks following major surgery, such as gastrectomy, and were recovered from any related toxicity More than 5 years since prior chemotherapy for malignancy other than GC. At least 4 weeks since prior radiotherapy * More than 5 years since prior biologic or hormonal therapy or immunotherapy for malignancy other than gastric carcinoma. Key
Exclusion criteria
* Pregnant or lactating females at any time during the study. * Known history of active CNS disease. * Uncontrolled ascites. * Concurrent anti-cancer therapy (chemotherapy, radiation therapy other than for pain relief, immunotherapy, biologic therapy, hormonal therapy or surgery) while taking investigational treatment. * Gastric carcinoid, epidermoid, sarcomas, or squamous cell carcinoma. * Prior palliative chemotherapy for the treatment of gastric cancer. * Prior treatment with oxaliplatin-based neoadjuvant or adjuvant chemotherapy completed \<12 months. * Malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease (such as Crohn's disease or ulcerative colitis). * Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure. * Uncontrolled infection. * History of other malignancy. However, subjects who were disease-free for 5 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, were eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at the Time of Primary Analysis | From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years) | Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing. |
| Overall Survival in All Randomized Participants at the Time of Primary Analysis | From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years) | Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Confirmed Complete Response (CR) or a Partial Response (PR) | From date of randomization till the date of the first documented response of CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | A participant was considered a responder if they had achieved either a complete response (CR), defined as the disappearance of all target and non-target lesions, or a partial response (PR), defined as at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, as assessed by the investigator and confirmed by radiographic imaging within four weeks of the initial observation. |
| Percentage of Participants With Clinical Benefit (CB) | From date of randomization till date of disease progression (PD) or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | Clinical Benefit (CB) was defined as evidence of a complete response (CR), partial response (PR), or stable disease (SD). CR referred to the disappearance of all target and non-target lesions, PR to at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, and SD to neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, based on the smallest sum of diameters recorded since treatment initiation. All assessments were made by the investigator. |
| Time to Response (TTR) | From date of randomization till the first documented evidence of confirmed CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator. |
| Duration of Response (DOR) | From the time of the first documented evidence of a confirmed CR or PR until the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | Duration of Response (DOR) was defined as the time from the first documented evidence of a complete response (CR) or partial response (PR) until the first recorded sign of disease progression or death from any cause. According to RECIST, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Those who received non-study anti-cancer therapies before progression were also censored. |
| Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE) | From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its causal relationship. This included any unfavorable or unintended sign (such as abnormal lab findings), symptom, or disease, whether new or worsened. A Serious Adverse Event (SAE) was defined as any such occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury. |
| Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its relationship to the product. This included any unfavorable or unintended sign (such as abnormal lab results), symptom, or disease, whether new or worsened. The severity of AEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity). |
| Overall Survival at the Time of Final Analysis | From date of randomization till death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing. |
| Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | The EORTC QLQ-C30 is a comprehensive questionnaire developed for assessing the quality of life of cancer patients across different aspects including function scales namely physical, role, cognitive, emotional and social; symptom scales such as fatigue, pain, nausea and vomiting; and a global scale pronouncing overall health status. Its scoring method involves a 4-point Likert scale (ranging from 1 'Not at all' to 4 'Very Much'). Domain scores are calculated by averaging the items within the respective domain and then linearly transforming the score to fit within a 0-100 scale to finalize the scores. In terms of interpretation, a high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. |
| Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | The QLQ-STO22 consists of 22 items divided into five subscales: dysphagia, pain, reflux, eating restrictions and anxiety, as well as single items addressing dry mouth, body image, taste, and hair loss. Each item is answered on a 4-point scale, ranging from 1 (not at all) to 4 (very much). Raw scores for each subscale or single item are calculated by averaging the scores of the individual items that make up the scale. These scores are then linearly transformed to range from 0 to 100. In terms of interpretation, a higher score indicates a worse quality of life concerning the specific symptoms assessed. |
| Mean Change From Baseline in Utility Score (Health Utility Index) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire | From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | The EQ-5D is a standardized instrument developed by the EuroQoL Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Utility Score (Health Utility Index) is derived from the five dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has levels indicating severity (e.g., 1 = no problems, 2 = some problems, 3 = extreme problems). These combinations form a health state, which is then converted into a single index value using a country-specific value set. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1.0, where: 1.0 = perfect health, 0 = death and \< 0 = health states considered worse than death. |
| Mean Change From Baseline in Thermometer Score (EQ VAS) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire | From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | The EQ-5D is a standardized instrument developed by the EuroQol Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Thermometer Score is a self-rated health score using a vertical visual analogue scale , where respondents rate their overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health). |
| Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | The severity of chemistry parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Chemistry data included: Alanine aminotransferase (ALT), Albumin, Alkaline phosphatases (ALP), Aspartate aminotransferase (AST), Calcium (hypercalcemia), Calcium (hypocalcemia), Creatine Kinase (CK), Creatine, Glucose (hyperglycemia), Glucose (hypoglycemia), Magnesium (hypermagnesemia), Magnesium (hypomagnesemia), Potassium (hyperkalemia), Potassium (hypokalemia), Sodium (hypernatremia), Sodium (hyponatremia) and Total Bilirubin. |
| Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | The severity of hematologic parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Hematology data included: Hemoglobin, Platelet count, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) and White Blood Cell count. |
| Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | A Serious Adverse Event (SAE) was defined as any such occurrence that resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury. The severity of SAEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity). |
| Progression Free Survival (PFS) | From date of randomization till the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years) | Progression-Free Survival (PFS) was defined as the time from randomization to the earliest occurrence of disease progression or death from any cause. Per RECIST v1.0, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants with symptomatic progression, even without radiological confirmation, were also counted. Those who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Participants who received non-study anti-cancer therapies before progression were also censored. |
Countries
Argentina, Brazil, Canada, Chile, China, Estonia, Hong Kong, Hungary, India, Israel, Italy, Mexico, Netherlands, Peru, Poland, Puerto Rico, Russia, South Korea, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
This study was conducted at 186 centers in 21 countries in North America (Canada and US), Asia (China, Hong Kong, Korea and Taiwan), and Rest of World (ROW) (Argentina, Brazil, Chile, Estonia, Hungary, India, Israel, Italy, Mexico, Netherlands, Peru, Poland, Russian Federation, Turkey, and Ukraine).
Pre-assignment details
Participants were randomized into one of two treatment arms: CapeOx plus lapatinib (the experimental arm) or CapeOx plus placebo (the control arm) using a 1:1 randomization.
Participants by arm
| Arm | Count |
|---|---|
| CapeOx Plus Lapatinib Participants received a combination therapy consisting of:
1. Oxaliplatin (Ox): 130 mg/m² intravenously on Day 1 of each 21-day cycle, for up to 8 cycles.
2. Capecitabine (Cape): 1700 mg/m² per day, taken orally in two divided doses from the evening of Day 1 to the morning of Day 15 (28 doses per cycle), followed by a minimum 6.5-day rest period. The dose could be increased to 2000 mg/m²/day after the first cycle at the investigator's discretion.
3. Lapatinib: 1250 mg orally once daily, starting on Day 1 and continued daily throughout the cycle, including the rest period.
After discontinuing oxaliplatin, capecitabine and lapatinib were continued until disease progression, unacceptable toxicity, or withdrawal of consent. | 272 |
| CapeOx Plus Placebo Participants received a combination therapy consisting of:
1. Oxaliplatin (Ox): 130 mg/m² intravenously on Day 1 of each 21-day cycle, for up to 8 cycles.
2. Capecitabine (Cape): 1700 mg/m² per day, taken orally in two divided doses from the evening of Day 1 to the morning of Day 15 (28 doses per cycle), followed by a minimum 6.5-day rest period. The dose could be increased to 2000 mg/m²/day after the first cycle at the investigator's discretion.
3. Lapatinib matching placebo: Taken orally once daily starting on Day 1 and continued throughout each cycle, including the rest period.
After discontinuing oxaliplatin, capecitabine and the lapatinib placebo were continued until disease progression, unacceptable toxicity, or withdrawal of consent. | 273 |
| Total | 545 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Ongoing: In Follow Up | 1 | 0 |
| Overall Study | Ongoing: On Study Treatment | 1 | 0 |
| Overall Study | Other protocol defined stopping criteria | 17 | 17 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Sponsor decision | 1 | 0 |
| Overall Study | Subject decided to withdraw from the study | 4 | 15 |
| Overall Study | Subject reached protocol defined stopping criteria | 1 | 0 |
Baseline characteristics
| Characteristic | CapeOx Plus Placebo | Total | CapeOx Plus Lapatinib |
|---|---|---|---|
| Age, Continuous | 58.5 Years STANDARD_DEVIATION 11.23 | 58.9 Years STANDARD_DEVIATION 11.21 | 59.4 Years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized African American/African Heritage (Hrtg) | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Central/South Asian Hrtg | 3 Participants | 14 Participants | 11 Participants |
| Race/Ethnicity, Customized Japanese/East Asian Hrtg/South East Asian Hrtg | 114 Participants | 226 Participants | 112 Participants |
| Race/Ethnicity, Customized White | 150 Participants | 294 Participants | 144 Participants |
| Sex: Female, Male Female | 73 Participants | 139 Participants | 66 Participants |
| Sex: Female, Male Male | 200 Participants | 406 Participants | 206 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 42 / 272 | 40 / 273 | 199 / 230 | 189 / 233 |
| other Total, other adverse events | 243 / 270 | 214 / 267 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 73 / 270 | 54 / 267 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival at the Time of Primary Analysis
Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Time frame: From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years)
Population: Primary Efficacy (PE) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CapeOx Plus Lapatinib | Overall Survival at the Time of Primary Analysis | 12.2 Months |
| CapeOx Plus Placebo | Overall Survival at the Time of Primary Analysis | 10.5 Months |
Comparison: Primary Analysis: OS (PE population)p-value: 0.349295% CI: [0.73, 1.12]Log Rank
Primary
Overall Survival in All Randomized Participants at the Time of Primary Analysis
Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Time frame: From date of randomization till death due to any cause, assessed up the cut-off date for Primary Analysis (24-Sep-2012) (average of 4 years)
Population: Intent-to-Treat (ITT) Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CapeOx Plus Lapatinib | Overall Survival in All Randomized Participants at the Time of Primary Analysis | 11.9 Months |
| CapeOx Plus Placebo | Overall Survival in All Randomized Participants at the Time of Primary Analysis | 10.4 Months |
Comparison: Primary Analysis: OS (ITT population)p-value: 0.324495% CI: [0.74, 1.1]Log Rank
Secondary
Duration of Response (DOR)
Duration of Response (DOR) was defined as the time from the first documented evidence of a complete response (CR) or partial response (PR) until the first recorded sign of disease progression or death from any cause. According to RECIST, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Those who received non-study anti-cancer therapies before progression were also censored.
Time frame: From the time of the first documented evidence of a confirmed CR or PR until the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population. Only those participants who had a confirmed CR or PR were analyzed for duration of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CapeOx Plus Lapatinib | Duration of Response (DOR) | 7.3 Months |
| CapeOx Plus Placebo | Duration of Response (DOR) | 5.6 Months |
Secondary
Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale
The QLQ-STO22 consists of 22 items divided into five subscales: dysphagia, pain, reflux, eating restrictions and anxiety, as well as single items addressing dry mouth, body image, taste, and hair loss. Each item is answered on a 4-point scale, ranging from 1 (not at all) to 4 (very much). Raw scores for each subscale or single item are calculated by averaging the scores of the individual items that make up the scale. These scores are then linearly transformed to range from 0 to 100. In terms of interpretation, a higher score indicates a worse quality of life concerning the specific symptoms assessed.
Time frame: From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population. Only those participants contributing data at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Dysphagia scale | 3.4 Scores on a scale | Standard Deviation 22.99 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Anxiety scale | -2.9 Scores on a scale | Standard Deviation 27.42 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Reflux scale | -1.4 Scores on a scale | Standard Deviation 21.86 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Dry mouth scale | 2.8 Scores on a scale | Standard Deviation 31.13 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Pain scale | -1.5 Scores on a scale | Standard Deviation 22.2 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Taste scale | 4.5 Scores on a scale | Standard Deviation 37.37 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Eating restrictions scale | 1.2 Scores on a scale | Standard Deviation 27.83 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Body image scale | -3.3 Scores on a scale | Standard Deviation 37.68 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Hair loss scale | -16.7 Scores on a scale | Standard Deviation 23.57 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Eating restrictions scale | -3.2 Scores on a scale | Standard Deviation 22.11 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Hair loss scale | 0.0 Scores on a scale | Standard Deviation 33.33 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Dysphagia scale | -3.1 Scores on a scale | Standard Deviation 16.92 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Pain scale | -0.6 Scores on a scale | Standard Deviation 18.71 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Reflux scale | -4.1 Scores on a scale | Standard Deviation 18.48 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Body image scale | -1.9 Scores on a scale | Standard Deviation 30.66 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Anxiety scale | -7.5 Scores on a scale | Standard Deviation 24.38 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Dry mouth scale | 1.9 Scores on a scale | Standard Deviation 32 |
| CapeOx Plus Placebo | Mean Change From Baseline in the EORTC Quality of Life (QOL) Questionnaire of Stomach 22 (QLQ-STO22) Scales/Items Score Scale | Taste scale | 9.2 Scores on a scale | Standard Deviation 32.03 |
Secondary
Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores
The EORTC QLQ-C30 is a comprehensive questionnaire developed for assessing the quality of life of cancer patients across different aspects including function scales namely physical, role, cognitive, emotional and social; symptom scales such as fatigue, pain, nausea and vomiting; and a global scale pronouncing overall health status. Its scoring method involves a 4-point Likert scale (ranging from 1 'Not at all' to 4 'Very Much'). Domain scores are calculated by averaging the items within the respective domain and then linearly transforming the score to fit within a 0-100 scale to finalize the scores. In terms of interpretation, a high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Time frame: From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population. Only those participants contributing data at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Cognitive functioning | -7.4 Scores on a scale | Standard Deviation 21.41 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Financial difficulties | 0.0 Scores on a scale | Standard Deviation 29.81 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Global health status/QoL | -6.6 Scores on a scale | Standard Deviation 24.63 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Physical functioning | -9.4 Scores on a scale | Standard Deviation 25.61 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Role functioning | -8.9 Scores on a scale | Standard Deviation 34.64 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Emotional functioning | -3.8 Scores on a scale | Standard Deviation 27.37 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Social functioning | -4.9 Scores on a scale | Standard Deviation 32.54 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Fatigue | 5.5 Scores on a scale | Standard Deviation 26.42 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Nausea and vomiting | 3.3 Scores on a scale | Standard Deviation 27.69 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Pain | 4.9 Scores on a scale | Standard Deviation 30.48 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Dyspnoea | 6.7 Scores on a scale | Standard Deviation 26.61 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Insomnia | 0.0 Scores on a scale | Standard Deviation 33.33 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Appetite loss | -0.5 Scores on a scale | Standard Deviation 39.2 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Constipation | -0.6 Scores on a scale | Standard Deviation 32.18 |
| CapeOx Plus Lapatinib | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Diarrhoea | 4.4 Scores on a scale | Standard Deviation 29.49 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Financial difficulties | 0.6 Scores on a scale | Standard Deviation 24.16 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Dyspnoea | 7.8 Scores on a scale | Standard Deviation 27.7 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Diarrhoea | 1.1 Scores on a scale | Standard Deviation 23.95 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Fatigue | 5.6 Scores on a scale | Standard Deviation 25.3 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Insomnia | 3.3 Scores on a scale | Standard Deviation 35.09 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Global health status/QoL | -5.1 Scores on a scale | Standard Deviation 23.97 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Nausea and vomiting | 4.4 Scores on a scale | Standard Deviation 20.62 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Physical functioning | -9.6 Scores on a scale | Standard Deviation 22.33 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Constipation | -3.8 Scores on a scale | Standard Deviation 34.48 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Role functioning | -11.7 Scores on a scale | Standard Deviation 31.67 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Pain | 7.7 Scores on a scale | Standard Deviation 30.06 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Emotional functioning | -7.1 Scores on a scale | Standard Deviation 23.61 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Cognitive functioning | -10.4 Scores on a scale | Standard Deviation 21.98 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Appetite loss | 5.5 Scores on a scale | Standard Deviation 37.11 |
| CapeOx Plus Placebo | Mean Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Domain Scores | Social functioning | -0.5 Scores on a scale | Standard Deviation 26.52 |
Secondary
Mean Change From Baseline in Thermometer Score (EQ VAS) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire
The EQ-5D is a standardized instrument developed by the EuroQol Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Thermometer Score is a self-rated health score using a vertical visual analogue scale , where respondents rate their overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).
Time frame: From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population. Only those participants contributing data at the indicated time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CapeOx Plus Lapatinib | Mean Change From Baseline in Thermometer Score (EQ VAS) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire | -4.61 Scores on a scale | Standard Deviation 23.054 |
| CapeOx Plus Placebo | Mean Change From Baseline in Thermometer Score (EQ VAS) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire | -7.90 Scores on a scale | Standard Deviation 17.349 |
Secondary
Mean Change From Baseline in Utility Score (Health Utility Index) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire
The EQ-5D is a standardized instrument developed by the EuroQoL Group to measure health-related quality of life. It includes a descriptive system covering five dimensions and a Visual Analogue Scale (VAS), often referred to as the Thermometer Score. The Utility Score (Health Utility Index) is derived from the five dimensions of the EQ-5D descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has levels indicating severity (e.g., 1 = no problems, 2 = some problems, 3 = extreme problems). These combinations form a health state, which is then converted into a single index value using a country-specific value set. In the UK-based value set, the possible EQ-5D index utility values range from -0.594 to 1.0, where: 1.0 = perfect health, 0 = death and \< 0 = health states considered worse than death.
Time frame: From Baseline up to disease progression (PD), assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population. Only those participants contributing data at the indicated time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CapeOx Plus Lapatinib | Mean Change From Baseline in Utility Score (Health Utility Index) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire | -0.17 Scores on a scale | Standard Deviation 0.347 |
| CapeOx Plus Placebo | Mean Change From Baseline in Utility Score (Health Utility Index) in the EuroQoL-5 Dimensions (EQ-5D) Questionnaire | -0.07 Scores on a scale | Standard Deviation 0.328 |
Secondary
Overall Survival at the Time of Final Analysis
Overall Survival was defined as the time from randomization to death from any cause. Participants who had not died were censored at their follow-up visit, either because follow-up had ended or was still ongoing.
Time frame: From date of randomization till death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CapeOx Plus Lapatinib | Overall Survival at the Time of Final Analysis | 12.0 Months |
| CapeOx Plus Placebo | Overall Survival at the Time of Final Analysis | 10.4 Months |
Secondary
Percentage of Participants With a Confirmed Complete Response (CR) or a Partial Response (PR)
A participant was considered a responder if they had achieved either a complete response (CR), defined as the disappearance of all target and non-target lesions, or a partial response (PR), defined as at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, as assessed by the investigator and confirmed by radiographic imaging within four weeks of the initial observation.
Time frame: From date of randomization till the date of the first documented response of CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With a Confirmed Complete Response (CR) or a Partial Response (PR) | 131 Participants |
| CapeOx Plus Placebo | Percentage of Participants With a Confirmed Complete Response (CR) or a Partial Response (PR) | 94 Participants |
Secondary
Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE)
An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its causal relationship. This included any unfavorable or unintended sign (such as abnormal lab findings), symptom, or disease, whether new or worsened. A Serious Adverse Event (SAE) was defined as any such occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury.
Time frame: From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE) | On-Therapy Adverse Events (Any AE regardless of seriousness) | 255 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE) | On-Therapy Serious Adverse Events | 73 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE) | On-Therapy Adverse Events (Any AE regardless of seriousness) | 237 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Any On-therapy Adverse Event (AE) and Serious Adverse Event (SAE) | On-Therapy Serious Adverse Events | 54 Participants |
Secondary
Percentage of Participants With Clinical Benefit (CB)
Clinical Benefit (CB) was defined as evidence of a complete response (CR), partial response (PR), or stable disease (SD). CR referred to the disappearance of all target and non-target lesions, PR to at least a 30% reduction in the sum of the longest diameters of target lesions from baseline, and SD to neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, based on the smallest sum of diameters recorded since treatment initiation. All assessments were made by the investigator.
Time frame: From date of randomization till date of disease progression (PD) or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With Clinical Benefit (CB) | 199 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Clinical Benefit (CB) | 188 Participants |
Secondary
Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade
An Adverse Event (AE) was defined as any untoward medical occurrence in a participant that was temporally associated with the use of a medicinal product, regardless of its relationship to the product. This included any unfavorable or unintended sign (such as abnormal lab results), symptom, or disease, whether new or worsened. The severity of AEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).
Time frame: From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Safety population. Only participants with On-therapy AEs
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 2 | 85 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 4 | 17 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 1 | 43 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 5 | 16 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 3 | 94 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 5 | 9 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 2 | 78 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 3 | 69 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 4 | 25 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Adverse Event (AE) by Maximum Grade | Grade 1 | 56 Participants |
Secondary
Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade
A Serious Adverse Event (SAE) was defined as any such occurrence that resulted in death, was life-threatening, required hospitalization or its prolongation, caused disability or incapacity, led to a congenital anomaly or birth defect, or was a potential case of drug-induced liver injury. The severity of SAEs was graded according to NCI CTCAE version 3.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (death related to toxicity).
Time frame: From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Safety population. Only participants with on-therapy Serious Adverse Events (SAEs)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 3 | 37 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 4 | 13 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 1 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 5 | 14 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 2 | 6 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 5 | 8 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 2 | 4 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 3 | 21 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 4 | 18 Participants |
| CapeOx Plus Placebo | Percentage of Participants With On-therapy Serious Adverse Event (SAE) by Maximum Grade | Grade 1 | 3 Participants |
Secondary
Percentage of Participants With Worst-case On-therapy Chemistry Toxicities
The severity of chemistry parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Chemistry data included: Alanine aminotransferase (ALT), Albumin, Alkaline phosphatases (ALP), Aspartate aminotransferase (AST), Calcium (hypercalcemia), Calcium (hypocalcemia), Creatine Kinase (CK), Creatine, Glucose (hyperglycemia), Glucose (hypoglycemia), Magnesium (hypermagnesemia), Magnesium (hypomagnesemia), Potassium (hyperkalemia), Potassium (hypokalemia), Sodium (hypernatremia), Sodium (hyponatremia) and Total Bilirubin.
Time frame: From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Safety Population. Only those participants contributing data at the indicated time point were analyzed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 1 | 113 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 0 | 120 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 2 | 22 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 3 | 5 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 2 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 1 | 115 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 0 | 108 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 3 | 6 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 1 | 133 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 3 | 5 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 2 | 16 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 1 | 32 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 3 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 0 | 160 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 0 | 237 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 0 | 186 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 1 | 17 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 4 | 1 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 2 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 0 | 153 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 3 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 0 | 189 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 0 | 129 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 0 | 223 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 1 | 74 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 3 | 7 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 2 | 50 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 1 | 59 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 3 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 4 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 1 | 75 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 0 | 1 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 1 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 2 | 5 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 2 | 8 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 0 | 228 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 3 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 2 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 3 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 1 | 20 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 3 | 1 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 0 | 230 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 0 | 163 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 1 | 21 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 1 | 87 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 2 | 7 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 4 | 1 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 3 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 2 | 8 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 0 | 229 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 0 | 107 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 3 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 2 | 30 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 3 | 21 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 0 | 234 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 0 | 123 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 1 | 18 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 1 | 20 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 2 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 1 | 72 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 3 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 4 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 4 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 2 | 59 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 2 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 1 | 52 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 3 | 1 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 2 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 3 | 19 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 2 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 4 | 2 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 3 | 3 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 1 | 55 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 2 | 43 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 2 | 32 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 0 | 237 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 1 | 20 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 2 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 3 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 0 | 195 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 1 | 54 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 4 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 1 | 17 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 2 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 3 | 5 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 0 | 199 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 1 | 52 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 2 | 5 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 3 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 2 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 3 | 11 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hypokalemia) | Grade 4 | 1 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 0 | 153 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 3 | 4 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 3 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hypoglycemia) | Grade 3 | 1 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypermagnesemia) | Grade 0 | 234 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 4 | 4 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 1 | 42 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 2 | 33 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 3 | 3 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 4 | 5 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Magnesium (hypomagnesemia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 0 | 234 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 1 | 14 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 1 | 94 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 2 | 11 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alanine aminotransferase (ALT) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 0 | 140 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 1 | 66 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 2 | 48 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 3 | 4 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Albumin | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 0 | 114 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 1 | 109 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 2 | 25 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 3 | 12 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Alkaline phosphatases (ALP) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 0 | 93 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 1 | 142 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 2 | 21 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 3 | 6 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Aspartate aminotransferase (AST) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 0 | 242 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 1 | 19 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 2 | 1 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypercalcemia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 0 | 134 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 1 | 81 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 2 | 43 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 3 | 4 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Calcium (hypocalcemia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 0 | 3 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 1 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Potassium (hyperkalemia) | Grade 2 | 11 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 2 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 3 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatine Kinase (CK) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 0 | 228 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 1 | 33 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 2 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 3 | 1 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Creatinine | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 0 | 119 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 1 | 103 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Glucose (hyperglycemia) | Grade 3 | 8 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 0 | 234 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 1 | 20 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 2 | 5 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 3 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hypernatremia) | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 0 | 199 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 1 | 42 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 2 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Sodium (hyponatremia) | Grade 3 | 16 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Chemistry Toxicities | Total Bilirubin | Grade 0 | 178 Participants |
Secondary
Percentage of Participants With Worst-case On-therapy Hematologic Toxicities
The severity of hematologic parameters was graded according to NCI CTCAE version 3.0: Grade 0 (No adverse event or within normal limits), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life-threatening). Hematology data included: Hemoglobin, Platelet count, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) and White Blood Cell count.
Time frame: From the first dose of study medication until 30 days after the last dose, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Safety Population. Only those participants contributing data at the indicated time point were analyzed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 0 | 18 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 1 | 104 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 0 | 97 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 2 | 104 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 3 | 35 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 4 | 0 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 1 | 95 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 2 | 43 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 3 | 21 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 4 | 5 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 0 | 112 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 1 | 42 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 2 | 58 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 3 | 22 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 4 | 6 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 0 | 126 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 1 | 71 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 2 | 50 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 3 | 12 Participants |
| CapeOx Plus Lapatinib | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 4 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 4 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 0 | 22 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 4 | 2 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 0 | 127 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 0 | 116 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 4 | 1 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 1 | 121 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 3 | 4 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 2 | 93 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 1 | 45 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 3 | 27 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 0 | 136 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Hemoglobin | Grade 4 | 0 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 2 | 48 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 1 | 86 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 2 | 47 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 2 | 27 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Total Neutrophils (Total ANC - Total Absolute Neutrophil Count) | Grade 3 | 27 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | Platelet count | Grade 3 | 30 Participants |
| CapeOx Plus Placebo | Percentage of Participants With Worst-case On-therapy Hematologic Toxicities | White Blood Cell count | Grade 1 | 74 Participants |
Secondary
Progression Free Survival (PFS)
Progression-Free Survival (PFS) was defined as the time from randomization to the earliest occurrence of disease progression or death from any cause. Per RECIST v1.0, progression was defined as at least a 20% increase in the sum of diameters of target lesions from the smallest recorded sum or the appearance of one or more new lesions. Participants with symptomatic progression, even without radiological confirmation, were also counted. Those who had neither progressed nor died were censored at their follow-up visit, either because follow-up had ended or was ongoing. Participants who received non-study anti-cancer therapies before progression were also censored.
Time frame: From date of randomization till the earliest date of disease progression or death due to any cause, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CapeOx Plus Lapatinib | Progression Free Survival (PFS) | 6.2 Months |
| CapeOx Plus Placebo | Progression Free Survival (PFS) | 5.4 Months |
Secondary
Time to Response (TTR)
Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.
Time frame: From date of randomization till the first documented evidence of confirmed CR or PR, assessed up the cut-off date for Final Analysis (03-Oct-2024) (average of 16 years)
Population: Primary Efficacy (PE) population. Only those participants who had a confirmed CR or PR were analyzed for time to response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CapeOx Plus Lapatinib | Time to Response (TTR) | 1.4 Months |
| CapeOx Plus Placebo | Time to Response (TTR) | 1.4 Months |