Colorectal Carcinoma
Conditions
Keywords
Metastatic colorectal cancer, Panitumumab, mFOLFOX6, First-line
Brief summary
The purpose of this study is to exploratorily examine efficacy and safety in the participants with chemotherapy-naïve unresectable, advanced/recurrent colorectal carcinoma of Kirsten rat sarcoma-2 virus (KRAS) wild-type who have been treated with 6 cycles (2 weeks/cycle) of first-line mFOLFOX6 + panitumumab combination therapy and then assigned to two groups i.e., a group receiving 5-FU/LV + panitumumab combination therapy and a group receiving mFOLFOX6 + panitumumab combination therapy.
Detailed description
The drug being tested in this study is called panitumumab. Panitumumab is being tested to treat people who have advanced/recurrent colorectal carcinoma of KRAS wild-type. This study will look at the efficacy and safety of 5-FU/LV + panitumumab(Pmab) combination therapy or mFOLFOX6 + Pmab combination therapy in the participants. The study will enroll 164 patients. All participants will receive 6 cycles of Protocol Treatment \[1\]: Pmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m\^2, DIV, at Day 1, l LV 200 mg/m\^2, DIV, at Day 1, 5-FU 400 mg/m\^2, IV, at Day 1, 5-FU 2400 mg/m\^2, CIV, at Day 2 once every two weeks from cycle 1 through cycle 6. Then they will be randomly assigned (by chance, like flipping a coin) to one of the treatment groups. * Group A * Group B This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 20 months.
Interventions
oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for enrollment: 1. Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer) 2. Participants with measurable lesion(s) according to the RECIST ver. 1.1 3. Participants who have not received chemotherapy for colorectal cancer. Participants who experience relapse more than 6 months after the final dose of perioperative adjuvant chemotherapy with fluoropyrimidine agents may be enrolled. 4. Aged ≥ 20 years at the time of enrollment 5. Participants classified as KRAS wild-type. However, the criteria will be changed to all patients who are verified to be of KRAS and NRAS wild-type when the KRAS and NRAS tests come to be covered by National Health Insurance, and the tests become feasible at medical institutions. 6. Participants who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment 1. Neutrophil count ≥ 1.5 × 10\^3/μL 2. White blood cell count ≥ 3.0 × 10\^3/μL 3. Platelet count ≥ 10.0 × 10\^4/μL 4. Hemoglobin ≥ 9.0 g/dL 5. Total bilirubin ≤ 2.0 mg/dL 6. AST ≤ 100 U/L (≤ 200 U/L if liver metastases are present) 7. ALT ≤ 100 U/L (≤ 200 U/L if liver metastases are present) 8. Serum creatinine ≤ 1.5 mg/dL 7. Participants who are assessed at Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) of 0 or 1 8. Life expectancy of ≥ 6 months after enrollment 9. Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment Inclusion criteria for randomization: 1. Participants who have received 6 cycles of mFOLFOX6 + panitumumab combination therapy 2. Participants who are assessed at ECOG P.S. of 0-1 in the 6th cycle. 3. Participants for whom PD or not evaluable has been denied on the RECIST 1.1 based on imaging tests conducted after the day of administration in the 6th cycle within 14 days (2 weeks).
Exclusion criteria
for enrollment: 1. Radiotherapy received for a measurable lesion 2. Radiotherapy received within 28 days (4 weeks) prior to enrollment for a lesion other than measurable lesions. However, treatment to relieve pain associated with metastatic bone tumors was allowed. 3. Known brain metastasis or strongly suspected of brain metastasis 4. Synchronous cancers or metachronous cancers with a disease-free period of ≤ 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection (esophageal, stomach, and cervical cancer, non-melanoma skin cancer, bladder cancer, etc.). 5. Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.) 6. Participants who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy 7. Active hemorrhage requiring blood transfusion 8. Disease requiring systemic steroids for treatment (excluding topical steroids) 9. Intestinal resection and colostomy within 2 weeks prior to enrollment 10. History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.) 11. Serious drug hypersensitivity 12. Local or systemic active infection requiring treatment, or fever indicating infection 13. Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment) 14. Active hepatitis B and/or active hepatitis C 15. Known human immunodeficiency virus infection 16. Other patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization | Up to 9 months after randomization | PFS rate was defined as the gross percentage of participants who survived with no evidence of progression from the day of randomization (Day 0) until 9 months after Day 0. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 31 months | OS was defined as the time from the day of randomization (Day 0) until death by all causes. |
| Response Rate (RR) | Up to approximately 31 months | RR was defined as the percentage of participants who had shown complete response (CR) or partial response (PR) as the best overall response in accordance with the RECIST 1.1 criteria after randomization. The best overall response was CR, followed by PR, stable disease (SD), progressive disease (PD), and not evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization., SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). |
| Time to Treatment Failure (TTF) | Up to approximately 31 months | TTF was defined as the time from the day of randomization (Day 0) until the day of protocol treatment discontinuation determination, the day of PD decision during protocol treatment, or death from any cause, whichever came the earliest. |
| Progression-Free Survival (PFS) | Up to approximately 31 months | The PFS is the period from the date of randomization (Day 0) until the date of judgment of progression from the date of randomization, or until death by all causes, whichever comes first. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. |
| Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) | Peripheral neuropathy was defined as events classified with a preferred term (PT) of peripheral neuropathy according to Standardized MedDRA Queries. |
| Percentage of Participants With Grade 3 or Higher Skin Toxicity | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) | Skin toxicity was defined as events classified with an system organ class of Skin and subcutaneous tissue disorders or a preferred term of paronychia. |
| Percentage of Participants With Adverse Events | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 72 investigative sites in Japan from 16 October 2014 to 31 March 2017 (as Primary Completion Date). After that, overall study completion of this study was occurred on 31 August 2017.
Pre-assignment details
Participants with a diagnosis of colorectal carcinoma were enrolled to receive protocol treatment (1) up to cycle 6 followed by randomization, received 1 out of 2 treatments from protocol treatment (2) group A and group B.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Participants who received Panitumumab (Pmab) 6 mg/kg, intravenous drip infusion (DIV), at Day 1, oxaliplatin (OXA) 85 mg/m\^2, DIV, at Day 1, levofolinate (l LV) 200 mg/m\^2, DIV, at Day 1, fluorouracil (5-FU) 400 mg/m\^2, intravenous (IV) at Day 1, 5-FU 2400 mg/m\^2, continuous intravenous infusion (CIV), at Day 2 once every two weeks from cycle 1 through cycle 6 as protocol treatment 1 followed by either Pmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m\^2, DIV, at Day 1, l LV 200 mg/m\^2, DIV, at Day 1, 5-FU 400 mg/m\^2, IV, at Day 1, 5-FU 2400 mg/m\^2, CIV, at Day 2 once every two weeks from cycle 7 until progressive disease or intolerance or Pmab 6 mg/kg, DIV, at Day 1, l LV 200 mg/m\^2, DIV, at Day 1, 5-FU 400 mg/m\^2, IV, at Day 1, 5-FU 2400 mg/m\^2, CIV, at Day 2 once every two weeks from cycle 7 until progressive disease or intolerance. | 164 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| In-between Period | Without Informed Consent | 1 | 0 | 0 |
| Protocol Treatment 1 Period | Adverse Event | 7 | 0 | 0 |
| Protocol Treatment 1 Period | Death During Protocol Treatment | 3 | 0 | 0 |
| Protocol Treatment 1 Period | Did not Meet Entrance Criteria | 1 | 0 | 0 |
| Protocol Treatment 1 Period | Lack of Efficacy | 15 | 0 | 0 |
| Protocol Treatment 1 Period | Major Protocol Deviation | 1 | 0 | 0 |
| Protocol Treatment 1 Period | Reason not specified | 8 | 0 | 0 |
| Protocol Treatment 1 Period | Surgery Aimed at Curative Resection | 9 | 0 | 0 |
| Protocol Treatment 1 Period | Voluntary Withdrawal | 6 | 0 | 0 |
| Protocol Treatment 2 Period | Adverse Event | 0 | 9 | 9 |
| Protocol Treatment 2 Period | Death During Protocol Treatment | 0 | 1 | 0 |
| Protocol Treatment 2 Period | Lack of Efficacy | 0 | 29 | 29 |
| Protocol Treatment 2 Period | Reason not specified | 0 | 4 | 4 |
| Protocol Treatment 2 Period | Surgery Aimed at Curative Resection | 0 | 5 | 7 |
| Protocol Treatment 2 Period | Voluntary Withdrawal | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population | — |
|---|---|---|
| Age, Continuous | 66.6 years STANDARD_DEVIATION 10.3 | — |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Cycle 1] 0 | 122 Participants | — |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Cycle 1] 1 | 42 Participants | — |
| Histological Type of Adenocarcinoma Moderately differentiated adenocarcinoma | 91 Participants | — |
| Histological Type of Adenocarcinoma Mucinous adenocarcinoma | 3 Participants | — |
| Histological Type of Adenocarcinoma Other | 8 Participants | — |
| Histological Type of Adenocarcinoma Poorly differentiated adenocarcinoma | 15 Participants | — |
| Histological Type of Adenocarcinoma Well differentiated adenocarcinoma | 47 Participants | — |
| History of Preoperative and/or Postoperative Adjuvant (Adj) Chemotherapy (CT) Had History of Pre/Postoperative Adj CT | 13 Participants | — |
| History of Preoperative and/or Postoperative Adjuvant (Adj) Chemotherapy (CT) Had No History of Pre/Postoperative Adj CT | 151 Participants | — |
| History of Radiotherapy Had History of Radiotherapy | 1 Participants | — |
| History of Radiotherapy Had No History of Radiotherapy | 163 Participants | — |
| History of Surgery Had History of Surgery | 113 Participants | — |
| History of Surgery Had No History of Surgery | 51 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Ascending colon | 15 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Cecum | 8 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Descending colon | 4 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Rectosigmoid | 12 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Rectum | 42 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Sigmoid colon | 43 Participants | — |
| Information on Primary Lesion: Primary Lesion Site Transverse colon | 10 Participants | — |
| Information on Primary Lesion: Single, Multiple or Unknown Multiple | 4 Participants | — |
| Information on Primary Lesion: Single, Multiple or Unknown Single | 120 Participants | — |
| Information on Primary Lesion: Single, Multiple or Unknown Unknown | 40 Participants | — |
| Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing Mutant-type | 10 Participants | — |
| Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing Unknown | 2 Participants | — |
| Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing Wild Type (WT) | 152 Participants | — |
| Number of Metastatic Organs at Enrollment 0 | 3 Participants | — |
| Number of Metastatic Organs at Enrollment 1 | 72 Participants | — |
| Number of Metastatic Organs at Enrollment ≥2 | 89 Participants | — |
| Number of Participants without Curative Resection During Protocol Treatment 1 | 164 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Japan | 164 participants | — |
| Sex: Female, Male Female | 55 Participants | — |
| Sex: Female, Male Male | 109 Participants | — |
| Treatment Status for Protocol Treatment 1: Postponed or Not Postponed Not Postponed | 43 Participants | — |
| Treatment Status for Protocol Treatment 1: Postponed or Not Postponed Postponed | 121 Participants | — |
| Treatment Status for Protocol Treatment 1: Reduced or Not Reduced Not Reduced | 105 Participants | — |
| Treatment Status for Protocol Treatment 1: Reduced or Not Reduced Reduced | 59 Participants | — |
| Type of Metastatic Organs at Enrollment Adrenal gland | 2 Participants | — |
| Type of Metastatic Organs at Enrollment Bone | 9 Participants | — |
| Type of Metastatic Organs at Enrollment Liver | 119 Participants | — |
| Type of Metastatic Organs at Enrollment Lung | 57 Participants | — |
| Type of Metastatic Organs at Enrollment Lymph node | 60 Participants | — |
| Type of Metastatic Organs at Enrollment Other | 13 Participants | — |
| Type of Metastatic Organs at Enrollment Peritoneum | 28 Participants | — |
| Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 Grade 2 | 21 Participants | — |
| Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 Grade ≥3 | 40 Participants | — |
| Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 None | 103 Participants | — |
| Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 Grade 1 | 51 Participants | — |
| Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 Grade 2 | 12 Participants | — |
| Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 Grade ≥3 | 1 Participants | — |
| Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 None | 100 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 56 | 0 / 54 |
| other Total, other adverse events | 47 / 56 | 45 / 54 |
| serious Total, serious adverse events | 20 / 56 | 18 / 54 |
Outcome results
Primary
Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization
PFS rate was defined as the gross percentage of participants who survived with no evidence of progression from the day of randomization (Day 0) until 9 months after Day 0. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 9 months after randomization
Population: Full Analysis Set (FAS) was defined as all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization | 46.4 percentage of participants |
| Group B | Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization | 47.4 percentage of participants |
95% CI: [-17.2, 19]
Secondary
Overall Survival (OS)
OS was defined as the time from the day of randomization (Day 0) until death by all causes.
Time frame: Up to approximately 31 months
Population: FAS was defined as all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Overall Survival (OS) | NA months |
| Group B | Overall Survival (OS) | NA months |
p-value: 0.348595% CI: [0.69, 2.88]Regression, Multivariable Cox
Secondary
Percentage of Participants With Adverse Events
Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.
Time frame: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)
Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Adverse Events | 100 percentage of participants |
| Group B | Percentage of Participants With Adverse Events | 100 percentage of participants |
Secondary
Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade
An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time frame: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)
Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 0 percentage of participants |
| Group A | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 19.6 percentage of participants |
| Group A | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3, 4 and 5 | 80.4 percentage of participants |
| Group B | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 1 | 0 percentage of participants |
| Group B | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 2 | 27.8 percentage of participants |
| Group B | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | Grade 3, 4 and 5 | 72.2 percentage of participants |
Secondary
Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy
Peripheral neuropathy was defined as events classified with a preferred term (PT) of peripheral neuropathy according to Standardized MedDRA Queries.
Time frame: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)
Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy | 30.4 percentage of participants |
| Group B | Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy | 3.7 percentage of participants |
Secondary
Percentage of Participants With Grade 3 or Higher Skin Toxicity
Skin toxicity was defined as events classified with an system organ class of Skin and subcutaneous tissue disorders or a preferred term of paronychia.
Time frame: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)
Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Percentage of Participants With Grade 3 or Higher Skin Toxicity | Skin and subcutaneous tissue disorders | 17.9 percentage of participants |
| Group A | Percentage of Participants With Grade 3 or Higher Skin Toxicity | Paronychia | 7.1 percentage of participants |
| Group B | Percentage of Participants With Grade 3 or Higher Skin Toxicity | Skin and subcutaneous tissue disorders | 18.5 percentage of participants |
| Group B | Percentage of Participants With Grade 3 or Higher Skin Toxicity | Paronychia | 9.3 percentage of participants |
Secondary
Progression-Free Survival (PFS)
The PFS is the period from the date of randomization (Day 0) until the date of judgment of progression from the date of randomization, or until death by all causes, whichever comes first. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to approximately 31 months
Population: FAS was defined as all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Progression-Free Survival (PFS) | 9.1 months |
| Group B | Progression-Free Survival (PFS) | 9.3 months |
p-value: 0.734995% CI: [0.6, 1.43]Regression, Multivariable Cox
Secondary
Response Rate (RR)
RR was defined as the percentage of participants who had shown complete response (CR) or partial response (PR) as the best overall response in accordance with the RECIST 1.1 criteria after randomization. The best overall response was CR, followed by PR, stable disease (SD), progressive disease (PD), and not evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization., SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time frame: Up to approximately 31 months
Population: FAS was defined as all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Response Rate (RR) | 80.4 percentage of participants |
| Group B | Response Rate (RR) | 87.7 percentage of participants |
Secondary
Time to Treatment Failure (TTF)
TTF was defined as the time from the day of randomization (Day 0) until the day of protocol treatment discontinuation determination, the day of PD decision during protocol treatment, or death from any cause, whichever came the earliest.
Time frame: Up to approximately 31 months
Population: FAS was defined as all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Time to Treatment Failure (TTF) | 8.1 months |
| Group B | Time to Treatment Failure (TTF) | 6.1 months |
p-value: 0.590195% CI: [0.6, 1.33]Regression, Multivariable Cox