Ovarian Cancer
Conditions
Brief summary
This two-part, multicenter study will evaluate the safety, tolerability and efficacy of pertuzumab in combination with standard chemotherapy in women with recurrent platinum-resistant epithelial ovarian cancer. In the non-randomized Part 1 safety run-in, participants will receive pertuzumab plus either topotecan or paclitaxel. In the randomized, double-blind Part 2 of the study, participants will receive either pertuzumab or placebo in combination with chemotherapy (topotecan, paclitaxel, or gemcitabine).
Interventions
Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.
Participants administered paclitaxel at a dosage of 80 mg/m\^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.
DRUGPertuzumab
Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.
DRUGPlacebo
Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.
DRUGTopotecan (Chemotherapy)
Participants administered topotecan at a dosage of 1.25 mg/m\^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, and/or fallopian tube cancer that is platinum-resistant or refractory * Low Human epidermal growth factor receptor (HER) 3 messenger ribonucleic acid (mRNA) expression * At least one measurable and/or non-measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Left ventricular ejection fraction (LVEF) greater than or equal to (\>/=) 50 percent (%) * Negative serum pregnancy test in women of childbearing potential * Women of childbearing potential must agree to use effective contraception as defined by protocol during and for at least 6 months post study treatment
Exclusion criteria
* Non-epithelial tumors * Ovarian tumors with low malignant potential (borderline tumors) * History of other malignancy of prognostic relevance within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma, or tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the breast * Previous treatment with more than 2 chemotherapy regimens * Any prior radiotherapy to the pelvis or abdomen * History or evidence on physical/neurological examination of central nervous system disease unrelated to cancer (uncontrolled seizures), unless adequately treated with standard medical therapy * Pre-existing peripheral neuropathy \>/= common toxicity criteria (CTC) grade 2 (applicable for paclitaxel cohort only) * Inadequate organ function * Uncontrolled hypertension or clinically significant cardiovascular disease * Current known infection with human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV), or hepatitis C virus (HCV) * Current chronic daily treatment with corticosteroids (\>/= 10 mg per day of methylprednisolone or equivalent), excluding inhaled steroids * History of receiving any investigational treatment within 28 days prior to first study drug administration * For Part 2 of the trial: prior enrollment into Part 1 of the trial * Concurrent participation in any therapeutic clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Adverse Events (AEs) | Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment) | An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO) | Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) | PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: PFS Assessed by the Investigator | Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression) | PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day. |
| Part 2: Progression-free Survival (PFS) Assessed by the Investigator | Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) | PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. |
| Part 1- Objective Response Rate (ORR) | Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression) | ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Part 2: Percentage of Participants With Adverse Events (AEs) | Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment) | An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Part 2: Overall Survival | Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) | Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause |
| Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Baseline (assessed at baseline and every 9 weeks from randomization until disease progression) | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life. |
| Part 2- Objective Response Rate (ORR) | Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) | ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Countries
Austria, Belgium, Denmark, France, Germany, Italy, Netherlands, Norway, Spain, Sweden
Participant flow
Pre-assignment details
A total of 208 participants were entered into the study, 52 participants in Part 1, and 156 participants in Part 2 of the study. Of these, 203 received treatment with pertuzumab or pertuzumab-placebo (50 participants in Part 1 and 153 participants in Part 2).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Pertuzumab + Topotecan Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. | 22 |
| Part 1: Pertuzumab + Paclitaxel Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. | 28 |
| Part 2: Pertuzumab+Chemotherapy Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion. | 78 |
| Part 2: Placebo+Chemotherapy Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigators assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion. | 78 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: Safety Run in Phase | Death | 15 | 20 | 0 | 0 |
| Part 1: Safety Run in Phase | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Part 1: Safety Run in Phase | Participants withdrawn consent | 1 | 1 | 0 | 0 |
| Part 2: Randomized Phase | Alive at data-cut | 0 | 0 | 13 | 7 |
| Part 2: Randomized Phase | Death | 0 | 0 | 62 | 68 |
| Part 2: Randomized Phase | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Part 2: Randomized Phase | Participant noncompliance | 0 | 0 | 0 | 1 |
| Part 2: Randomized Phase | Participant withdrew consent | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Part 1: Pertuzumab + Topotecan | Part 1: Pertuzumab + Paclitaxel | Part 2: Pertuzumab+Chemotherapy | Part 2: Placebo+Chemotherapy |
|---|---|---|---|---|---|
| Age, Customized Greater than (>)65 years | 90 participants | 7 participants | 11 participants | 38 participants | 34 participants |
| Age, Customized Less than or equal to (≤)65 years | 116 participants | 15 participants | 17 participants | 40 participants | 44 participants |
| Sex: Female, Male Female | 206 Participants | 22 Participants | 28 Participants | 78 Participants | 78 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 22 | 27 / 28 | 72 / 77 | 75 / 76 |
| serious Total, serious adverse events | 9 / 22 | 11 / 28 | 29 / 77 | 33 / 76 |
Outcome results
Primary
Part 1: Percentage of Participants With Adverse Events (AEs)
An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
Population: All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 1: Percentage of Participants With Adverse Events (AEs) | 95.5 percentage of participants |
| Part 1: Pertuzumab + Paclitaxel | Part 1: Percentage of Participants With Adverse Events (AEs) | 100.0 percentage of participants |
Primary
Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)
PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Population: ITT Population was defined as all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO) | 4.27 months |
| Part 1: Pertuzumab + Paclitaxel | Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO) | 2.74 months |
Comparison: The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan vs paclitaxel), previous anti-angiogenic therapy (yes versus no), and progression-free interval (PFI) since platinum therapy (\< 3 months versus 3-6 months). A hazard ratio \< 1 favored the pertuzumab + chemotherapy treatment arm.p-value: 0.498395% CI: [0.62, 1.27]2 sided log-rank
Secondary
Part 1- Objective Response Rate (ORR)
ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)
Population: All Treated participants with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 1- Objective Response Rate (ORR) | 14.3 percentage of participants |
| Part 1: Pertuzumab + Paclitaxel | Part 1- Objective Response Rate (ORR) | 25.0 percentage of participants |
Secondary
Part 1: PFS Assessed by the Investigator
PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.
Time frame: Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)
Population: All Treated population included all participants enrolled and treated in Part 1 of the study ('as treated' analysis) and who had received at least 1 dose of pertuzumab or chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 1: PFS Assessed by the Investigator | 4.07 months |
| Part 1: Pertuzumab + Paclitaxel | Part 1: PFS Assessed by the Investigator | 4.24 months |
Secondary
Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.
Time frame: Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)
Population: ITT population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Social (n=71, 73) | 70.7 units on a scale | Standard Deviation 30.01 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Dyspnoea (n=68, 73) | 22.5 units on a scale | Standard Deviation 28.47 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Role (n=70, 73) | 68.6 units on a scale | Standard Deviation 33.16 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Insomnia (n=69, 74) | 35.3 units on a scale | Standard Deviation 31.25 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Fatigue (n=71, 74) | 41.2 units on a scale | Standard Deviation 28.75 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Appetite loss (n=71, 73) | 24.9 units on a scale | Standard Deviation 30.19 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Cognitive (n=71, 73) | 81.2 units on a scale | Standard Deviation 25.34 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Constipation (n=69, 72) | 25.6 units on a scale | Standard Deviation 32.41 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Nausea and vomiting (n=72, 74) | 10.4 units on a scale | Standard Deviation 15.68 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Diarrhoea (n=69, 72) | 14.5 units on a scale | Standard Deviation 26.49 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Emotional (n=71, 73) | 59.5 units on a scale | Standard Deviation 24.03 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales:Financial difficulties(n=70,72 | 17.6 units on a scale | Standard Deviation 28.78 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Pain (n=72, 74) | 35.2 units on a scale | Standard Deviation 31.34 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Global health status / QoL scale (n=71, 72) | 54.1 units on a scale | Standard Deviation 24.99 |
| Part 1: Pertuzumab + Topotecan | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Physical (n=71, 74) | 71.1 units on a scale | Standard Deviation 22.77 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Global health status / QoL scale (n=71, 72) | 61.1 units on a scale | Standard Deviation 22.29 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Physical (n=71, 74) | 74.9 units on a scale | Standard Deviation 20.85 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Role (n=70, 73) | 69.4 units on a scale | Standard Deviation 32.4 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Emotional (n=71, 73) | 65.9 units on a scale | Standard Deviation 23.42 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Cognitive (n=71, 73) | 84.9 units on a scale | Standard Deviation 20.25 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Functional Scales: Social (n=71, 73) | 68.3 units on a scale | Standard Deviation 29.81 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Fatigue (n=71, 74) | 38.4 units on a scale | Standard Deviation 27.77 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Nausea and vomiting (n=72, 74) | 12.4 units on a scale | Standard Deviation 20.47 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Pain (n=72, 74) | 31.1 units on a scale | Standard Deviation 29.24 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Dyspnoea (n=68, 73) | 21.5 units on a scale | Standard Deviation 27.98 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Insomnia (n=69, 74) | 31.5 units on a scale | Standard Deviation 31.16 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Appetite loss (n=71, 73) | 21.0 units on a scale | Standard Deviation 26.36 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Constipation (n=69, 72) | 26.4 units on a scale | Standard Deviation 32.59 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales: Diarrhoea (n=69, 72) | 14.4 units on a scale | Standard Deviation 22.26 |
| Part 1: Pertuzumab + Paclitaxel | Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score | Symptomatic Scales:Financial difficulties(n=70,72 | 13.4 units on a scale | Standard Deviation 22.83 |
Secondary
Part 2- Objective Response Rate (ORR)
ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Population: ITT population with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 2- Objective Response Rate (ORR) | 14.8 percentage of participants |
| Part 1: Pertuzumab + Paclitaxel | Part 2- Objective Response Rate (ORR) | 8.7 percentage of participants |
p-value: 0.410295% CI: [6, 18.3]Fisher Exact
Secondary
Part 2: Overall Survival
Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause
Time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Population: ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 2: Overall Survival | 10.18 months |
| Part 1: Pertuzumab + Paclitaxel | Part 2: Overall Survival | 8.36 months |
Comparison: The stratified time-to-event analysis included the treatment group variable plus the following stratification factors: selected chemotherapy cohort (gemcitabine versus topotecan versus paclitaxel), previous angiogenic therapy (yes versus no) and PFI since platinum therapy (\<3 months versus 3-6 months).p-value: 0.59695% CI: [0.61, 1.32]2 sided log-rank
Secondary
Part 2: Percentage of Participants With Adverse Events (AEs)
An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
Population: Safety population included all participants who had received at least 1 dose of pertuzumab, pertuzumab-placebo, or chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 2: Percentage of Participants With Adverse Events (AEs) | 98.7 percentage of participants |
| Part 1: Pertuzumab + Paclitaxel | Part 2: Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
Secondary
Part 2: Progression-free Survival (PFS) Assessed by the Investigator
PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.
Time frame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Population: ITT Population included all randomized participants in the group to which they were randomly assigned ('as randomized' analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Pertuzumab + Topotecan | Part 2: Progression-free Survival (PFS) Assessed by the Investigator | 4.22 months |
| Part 1: Pertuzumab + Paclitaxel | Part 2: Progression-free Survival (PFS) Assessed by the Investigator | 3.94 months |