Squamous Cell Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Nab-paclitaxel, Albumin bound paclitaxel, Taxanes, Maintenance trials, Celgene, Abraxane, ABI-007, NSCLC, Non-Small Cell Lung Cancer, Cancer of the Lung, Carcinoma, Squamous Cell, Lung Neoplasms, Abound.sqm
Brief summary
Maintenance treatment of advanced stage squamous cell NSCLC. Phase III, randomized, open-label, multi-center study of nab-paclitaxel with best supportive care (BSC) or BSC alone as maintenance treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin as induction in subjects with stage IIIB/IV squamous cell NSCLC. Subjects who discontinued treatment from the maintenance part for any reason other than withdrawal of consent, lost to follow-up, or death, were entered into a Follow-up period that had a visit 28 days after progression or discontinuation. Those who entered Follow-up without progression continued with follow-up scans according to standard of care (SOC) until documentation of progression of disease. Additionally, subjects were followed for OS by phone approximately every 90 days for a minimum of 18 months, for up to approximately 5 years after the last subject was randomized.
Detailed description
The sponsor used 15 Sep 2017 as the database cut-off date.
Interventions
DRUGAbraxane (Induction)
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 15 of each 21-day cycle, administered as standard of care
DRUGCarboplatin (Induction)
6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion
DRUGAbraxane (Maintenance)
100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, administered as standard of care
OTHERBest Supportive Care (Maintenance)
The best palliative care per investigator (including but not limited to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding antineoplastic agents
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years of age at the time of signing the Informed Consent Form. 2. Understand and voluntarily provide written consent to the Informed Consent Form prior to conducting any study related assessments/procedures. 3. Able to adhere to the study visit schedule and other protocol requirements Disease Specific 4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell Non Small Cell Lung Cancer at study entry. 5. No other current active malignancy requiring anticancer therapy. 6. Radiographically documented measurable disease at study entry (as defined by the Response Evaluation Criteria In Solid Tumors \[RECIST\] v1.1 criteria). 7. No prior chemotherapy for the treatment of metastatic disease at study entry. Adjuvant chemotherapy is permitted providing cytotoxic chemotherapy was completed 12 months prior to starting the study and without disease recurrence. 8. Absolute neutrophil count ≥ 1500 cells/mm\^3. 9. Platelets ≥ 100,000 cells/mm\^3. 10. Hemoglobin ≥ 9 g/dL. 11. Aspartate transaminase/serum glutamic oxaloacetic transaminase, alanine transaminase/serum glutamic pyruvic transaminase ≤ 2.5 × upper limit of normal range or ≤ 5.0 × upper limit of normal range if liver metastases. 12. Total bilirubin ≤ 1.5 × upper limit of normal range except in cases of Gilbert's disease and liver metastases. 13. Creatinine ≤ 1.5 mg/dL. 14. Expected survival of \> 12 weeks for the Induction part of the study. 15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 16. For Maintenance part of the study, subjects must have received at least one dose of nab-paclitaxel in each of the 4 cycles during Induction Pregnancy 17. Females of childbearing potential \[defined as a sexually mature woman who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months)\] must: 1. agree to take a pregnancy test prior to starting study medication and throughout the study participation. 2. commit to complete abstinence from heterosexual contact, or agree to use medical doctor-approved contraception throughout the study without interruption, and while receiving study medication or for a longer period if required by local regulations. 18. Male subjects must: c. agree to complete abstinence from heterosexual contact or use a condom during sexual contact with a female of child bearing potential while receiving study medication and within 6 months after last dose of study medication, even if he has undergone a successful vasectomy. 19. Females must abstain from breastfeeding during study participation and 3 months after IP discontinuation.
Exclusion criteria
The presence of any of the following will exclude a subject from enrollment into the Induction and Maintenance parts of the study (except if specified at study entry only): 1. Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for ≥ 4 weeks prior to first dose of study drug). 2. Only evidence of disease is non-measurable at study entry. 3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events v4.0). 4. Venous thromboembolism within 6 months prior to signing Informed Consent Form. 5. Current congestive heart failure (New York Heart Association class II-IV). 6. History of the following within 6 months prior to first administration of a study drug: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder. 7. Treatment with any investigational product within 28 days prior to signing Informed Consent Form. 8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin. 9. Currently enrolled in any other clinical protocol or investigational trial that involved administration of experimental therapy and/or therapeutic devices. 10. Any other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol. 11. Subject has any other malignancy within 5 years prior to randomization. Exceptions include the following: squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b) - all treatments that should have been completed 6 months prior to signing informed consent form (ICF). 12. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting investigational product (IP), and/or from whom ≥ 30% of the bone marrow was irradiated. Prior radiation therapy to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed. 13. Pregnant and nursing females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance | From the date of randomization to the date of disease progression or death of any cause; up to data cut off date of 15 September 2017; up to 27.6 months | Progression-free survival is defined as the time in months from the date of randomization to the date of disease progression based on the investigator's assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by computerized axial tomography \[CT scan\], not including symptomatic deterioration) or death (any cause) on or prior to 01 Aug 2019. RECIST 1.1 Definition: - Complete response (CR) -disappearance of all target lesions; - Partial response (PR) -at least a 30% decrease in the sum of diameters of target lesions from baseline - Stable disease (SD) -neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase of lesions to qualify for progressive disease (PD) - Progressive Disease (PD) - At least a 20% increase in the sum of diameters of target lesions from nadir, and/or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study | Day 1 of treatment in the induction period and subsequent anticancer therapy, death or discontinuation up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study | Overall response was defined as the percentage of participants with a confirmed assessment of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and confirmed in no less than 28 days. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. RECIST 1.1 Definition: - Complete response-disappearance of all target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to \< 10 mm. - Partial response-at least a 30% decrease in the sum of diameters of target lesions from baseline. |
| Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study | Between Day 1 of the Induction Part through to the date of disease progression or death; up to 01 August 2019; the maximum treatment duration was 234.1 weeks for entire study | PFS was defined as the time in months from Day 1 of treatment for the Induction part to the date of disease progression according to RECIST 1.1 criteria (documented by CT-scan, not including symptomatic deterioration) or death (any cause) on or prior to 01 August 2019, whichever occurred earlier. RECIST 1.1 Definition: - Progressive Disease (PD) - At least a 20% increase in the sum of diameters of target lesions from nadir; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of new lesions is also considered progression. |
| Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study | Between Day 1 of treatment in the Induction Part to death from any cause; up to 01 August 2019; survival follow up was 55.89 months | Overall survival was defined as the time in months from Day 1 of treatment for the Induction part to death from any cause. Subjects who were alive at the time of analysis had their OS censored at the date or last contact of 01 August 2019, whichever was earlier. The last contact date was the date of the last record in the database, or if the subject was lost to follow-up, the last known date that the subject was alive. |
| Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) In Maintenance Beyond the Response in Induction | For the induction period the maximum treatment was 19 weeks for the maintenance period the maximum treatment was 150 weeks. | Overall response in the maintenance period was defined as the percentage of participants who showed an improvement in best overall response from stable disease (SD) or partial response (PR) during Induction to a Complete Response (CR) or PR during Maintenance according to RECIST 1.1 criteria and confirmed in no less than 28 days. Evaluation takes as reference the lesion measurement or status at the last tumor assessment before randomization to Maintenance. The 95% CI was calculated using Clopper-Pearson method. RECIST 1.1 Definition: - Complete response-disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. - Partial response-at least a 30% decrease in the sum of diameters of target lesions from baseline. - Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease. |
| Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance | From the date of randomization to death from any cause; up to 01 August 2019; survival follow up was 55.89 months | Overall survival was defined as the duration in months between randomization and death from any cause. Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off (01 August 2019 whichever was earlier. The last contact date was the date of the last record in the database, or if the subject was lost to follow-up, the last known date that the subject was alive. |
| Time to Confirmed Response During Induction and Over the Entire Study | Induction is from Day 1 to a maximum treatment time of 19 weeks; entire study from Day 1 Induction through Maintenance up to PD; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study | Time to confirmed complete or partial response (CR/PR) is defined as the time from day 1 of treatment in Induction to the first occurrence of confirmed CR/PR. Two timeframes are offered: - Time to confirmed response within the Induction timeframe. - Time to Confirmed Response Over the Entire Study, i.e. the time from Day 1 of treatment in Induction to the first occurrence of confirmed CR/PR any time during the study. Only participants with a confirmed CR or PR are included in this summary. |
| Kaplan-Meier Estimate for Duration of Response Over the Entire Study | Between Day 1 of the Induction Period through to the date of disease progression or death; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study. | Duration of overall response was measured from the time criteria were first met for CR/PR until the first date the recurrent or progressive disease (PD) was radiologically documented. Participants who did not have PD after the response were censored on the date of last tumor assessment. If a participant died before PD, the participant was censored on the date of death. |
| Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Day 1 of Induction up to Week 23 (maximum treatment in Induction plus 4 weeks if not continuing into Maintenance) | TEAE in the Induction part is defined as any adverse event (AE) with an onset on or after Day 1 of treatment for the Induction part, and on or before the day of randomization for subjects who entered into the Maintenance part, or, for subjects who did not enter into the Maintenance part, before the treatment discontinuation date plus 28 days or any serious AE which occurred thereafter but was determined to be related to any study drug by the investigator. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild, Grade 2 = Moderate Grade, 3 = Severe Grade, 4 = Life threatening, Grade 5 = Death. Relation to study drug was determined by the investigator. |
| Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | From Day 1 up to 01 August 2019; (maximum treatment length plus 28 days); the maximum treatment duration was 234.1 weeks for entire study | TEAE over entire study is defined as any adverse event (AE) with an onset on or after Day 1 of treatment for the Induction part, and before the treatment discontinuation date plus 28 days, or any serious AE which occurred thereafter but was determined to be related to any study drug by the investigator. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life threatening, Grade 5 = Death. Relation to study drug was determined by the investigator. |
| Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study | Induction is from Day 1 to a maximum treatment time of 19 weeks; entire study from Day 1 induction through maintenance up to PD; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study | Disease control rate was defined as the percentage of participants who had radiologic CR, PR or SD for \>= 6 weeks according to RECIST 1.1 criteria as determined by the investigator. Only participants with a confirmed CR/PR are included in this summary. Two timeframes are offered: - Time to confirmed response within the Induction timeframe. - Time to Confirmed Response Over the Entire Study, i.e. the time from Day 1 of treatment in Induction to the first occurrence of confirmed CR/PR any time during the study. RECIST 1.1 Definition: - CR- disappearance of all target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to \< 10 mm. - PR- at least a 30% decrease in the sum of diameters of target lesions from baseline; - SD- neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for PD. The 95% CI was calculated using Clopper-Pearson method. |
Countries
Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 87 sites in Germany, Italy, Spain, the United Kingdom and the United States.
Pre-assignment details
Participants with a response or stable disease during Induction were randomised 2:1 into investigative treatment (nab-paclitaxel plus best supportive care \[BSC\] or BSC only) stratified by disease stage, response during induction and Eastern Cooperative Oncology Group (ECOG) performance status.
Participants by arm
| Arm | Count |
|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) Maintenance Phase: Following randomization, participants in this treatment arm were administered nab-paclitaxel 100 mg/m\^2 by IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, plus best supportive care until disease progression. | 136 |
| Best Supportive Care (BSC) Maintenance Phase: Following randomization, participants in this treatment arm were administered best supportive care (only) until disease progression. | 66 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Induction | Adverse Event | 51 | 0 | 0 |
| Induction | Death | 21 | 0 | 0 |
| Induction | Induction Treatment Ongoing | 4 | 0 | 0 |
| Induction | Miscellaneous | 14 | 0 | 0 |
| Induction | Never treated | 7 | 0 | 0 |
| Induction | Progressive disease | 77 | 0 | 0 |
| Induction | Protocol Violation | 1 | 0 | 0 |
| Induction | Study terminated by sponsor | 12 | 0 | 0 |
| Induction | Symptomatic deterioration | 16 | 0 | 0 |
| Induction | Withdrawal by Subject | 22 | 0 | 0 |
| Maintenance | Adverse Event | 0 | 21 | 1 |
| Maintenance | Death | 0 | 3 | 2 |
| Maintenance | Other | 0 | 6 | 3 |
| Maintenance | Progressive disease | 0 | 84 | 47 |
| Maintenance | Protocol Violation | 0 | 0 | 1 |
| Maintenance | Symptomatic deterioration | 0 | 4 | 1 |
| Maintenance | Withdrawal by Subject | 0 | 6 | 5 |
| Survival Follow-up | Death | 0 | 78 | 45 |
| Survival Follow-up | Lost to Follow-up | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Nab-Paclitaxel + Best Supportive Care (BSC) | Best Supportive Care (BSC) |
|---|---|---|---|
| Age, Continuous | 67.0 years STANDARD_DEVIATION 8.7 | 67.1 years STANDARD_DEVIATION 9.02 | 66.8 years STANDARD_DEVIATION 8.06 |
| Age, Customized <65 years | 75 Participants | 48 Participants | 27 Participants |
| Age, Customized >=65 years | 127 Participants | 88 Participants | 39 Participants |
| Age, Customized <70 years | 120 Participants | 79 Participants | 41 Participants |
| Age, Customized >=70 years | 82 Participants | 57 Participants | 25 Participants |
| Age, Customized <75 years | 165 Participants | 110 Participants | 55 Participants |
| Age, Customized >=75 years | 37 Participants | 26 Participants | 11 Participants |
| Confirmed Histology Squamous cell carcinoma | 202 Participants | 136 Participants | 66 Participants |
| Confirmed Histology Squamous cell carcinoma not confirmed | 0 Participants | 0 Participants | 0 Participants |
| Disease Stage at Enrollment Stage IIIB | 26 Participants | 18 Participants | 8 Participants |
| Disease Stage at Enrollment Stage IV | 176 Participants | 118 Participants | 58 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0=fully active, no restriction | 60 Participants | 41 Participants | 19 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1=fully ambulatory; restricted strenuous activity | 142 Participants | 95 Participants | 47 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) >=2=ambulatory/self care; no work or worse | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 193 Participants | 132 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Overall Tumor Response at End of Induction Complete response | 3 Participants | 1 Participants | 2 Participants |
| Overall Tumor Response at End of Induction Not evaluable | 1 Participants | 0 Participants | 1 Participants |
| Overall Tumor Response at End of Induction Partial response | 134 Participants | 92 Participants | 42 Participants |
| Overall Tumor Response at End of Induction Progressive disease | 2 Participants | 2 Participants | 0 Participants |
| Overall Tumor Response at End of Induction Stable disease | 62 Participants | 41 Participants | 21 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 9 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 187 Participants | 125 Participants | 62 Participants |
| Sex: Female, Male Female | 72 Participants | 49 Participants | 23 Participants |
| Sex: Female, Male Male | 130 Participants | 87 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 80 / 420 | 82 / 130 | 48 / 62 |
| other Total, other adverse events | 417 / 420 | 122 / 130 | 45 / 62 |
| serious Total, serious adverse events | 177 / 420 | 32 / 130 | 13 / 62 |
Outcome results
Primary
Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance
Progression-free survival is defined as the time in months from the date of randomization to the date of disease progression based on the investigator's assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by computerized axial tomography \[CT scan\], not including symptomatic deterioration) or death (any cause) on or prior to 01 Aug 2019. RECIST 1.1 Definition: - Complete response (CR) -disappearance of all target lesions; - Partial response (PR) -at least a 30% decrease in the sum of diameters of target lesions from baseline - Stable disease (SD) -neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase of lesions to qualify for progressive disease (PD) - Progressive Disease (PD) - At least a 20% increase in the sum of diameters of target lesions from nadir, and/or the appearance of new lesions.
Time frame: From the date of randomization to the date of disease progression or death of any cause; up to data cut off date of 15 September 2017; up to 27.6 months
Population: Intent to treat (ITT) population of participants randomized to Maintenance. The ITT population in the Maintenance part included all randomized subjects regardless of whether the subject received any study drug or had any efficacy assessments collected.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance | 3.12 months |
| Best Supportive Care (BSC) | Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance | 2.60 months |
Comparison: 5% level of significance. Hazard ratio is based on stratified Cox proportional hazards regression model. The following stratification factors were evaluated in the sparse strata elimination algorithm: stage of disease (IIIB or IV) at diagnosis, ECOG performance status (0 or 1) at end of Induction, and tumor response (CR/PR or SD) at the end of Induction.p-value: 0.348695% CI: [0.61, 1.19]stratified log-rank test
Secondary
Kaplan-Meier Estimate for Duration of Response Over the Entire Study
Duration of overall response was measured from the time criteria were first met for CR/PR until the first date the recurrent or progressive disease (PD) was radiologically documented. Participants who did not have PD after the response were censored on the date of last tumor assessment. If a participant died before PD, the participant was censored on the date of death.
Time frame: Between Day 1 of the Induction Period through to the date of disease progression or death; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study.
Population: The ITT population of participants randomized to the maintenance period and had a confirmed partial or complete response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Kaplan-Meier Estimate for Duration of Response Over the Entire Study | 5.95 months |
| Best Supportive Care (BSC) | Kaplan-Meier Estimate for Duration of Response Over the Entire Study | 4.60 months |
Comparison: Hazard ratio was based on stratified Cox proportional hazards regression model. The following stratification factors were evaluated in the sparse strata elimination algorithm: stage of disease (IIIB or IV) at diagnosis, ECOG performance status (0 or 1) at the end of Induction, and tumor response (CR/PR or SD) at the end of Induction.95% CI: [0.59, 1.47]
Secondary
Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance
Overall survival was defined as the duration in months between randomization and death from any cause. Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off (01 August 2019 whichever was earlier. The last contact date was the date of the last record in the database, or if the subject was lost to follow-up, the last known date that the subject was alive.
Time frame: From the date of randomization to death from any cause; up to 01 August 2019; survival follow up was 55.89 months
Population: Intent to Treat population of participants randomized to maintenance.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance | 17.61 months |
| Best Supportive Care (BSC) | Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance | 12.16 months |
Comparison: 5% level of significance. Hazard ratio is based on stratified Cox proportional hazards regression model. The following stratification factors were evaluated in the sparse strata elimination algorithm: stage of disease (IIIB or IV) at diagnosis, ECOG performance status (0 or 1) at end of Induction, and tumor response (CR/PR or SD) at the end of Induction.p-value: 0.036595% CI: [0.47, 0.98]stratified log-rank test
Secondary
Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study
Overall survival was defined as the time in months from Day 1 of treatment for the Induction part to death from any cause. Subjects who were alive at the time of analysis had their OS censored at the date or last contact of 01 August 2019, whichever was earlier. The last contact date was the date of the last record in the database, or if the subject was lost to follow-up, the last known date that the subject was alive.
Time frame: Between Day 1 of treatment in the Induction Part to death from any cause; up to 01 August 2019; survival follow up was 55.89 months
Population: ITT population of participants randomized to Maintenance.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study | 20.57 months |
| Best Supportive Care (BSC) | Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study | 15.05 months |
Comparison: 5% level of significance. Hazard ratio is based on stratified Cox proportional hazards regression model. The following stratification factors were evaluated in the sparse strata elimination algorithm: stage of disease (IIIB or IV) at diagnosis, ECOG performance status (0 or 1) at end of Induction, and tumor response (CR/PR or SD) at the end of Induction.p-value: 0.038195% CI: [0.47, 0.98]stratified log-rank test
Secondary
Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study
PFS was defined as the time in months from Day 1 of treatment for the Induction part to the date of disease progression according to RECIST 1.1 criteria (documented by CT-scan, not including symptomatic deterioration) or death (any cause) on or prior to 01 August 2019, whichever occurred earlier. RECIST 1.1 Definition: - Progressive Disease (PD) - At least a 20% increase in the sum of diameters of target lesions from nadir; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of new lesions is also considered progression.
Time frame: Between Day 1 of the Induction Part through to the date of disease progression or death; up to 01 August 2019; the maximum treatment duration was 234.1 weeks for entire study
Population: Intent to treat population of participants randomized to Maintenance
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study | 6.47 months |
| Best Supportive Care (BSC) | Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study | 5.55 months |
Comparison: 5% level of significance. Hazard ratio is based on stratified Cox proportional hazards regression model. The following stratification factors were evaluated in the sparse strata elimination algorithm: stage of disease (IIIB or IV) at diagnosis, ECOG performance status (0 or 1) at end of Induction, and tumor response (CR/PR or SD) at the end of Induction.p-value: 0.416495% CI: [0.62, 1.22]stratified log-rank test
Secondary
Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period
TEAE in the Induction part is defined as any adverse event (AE) with an onset on or after Day 1 of treatment for the Induction part, and on or before the day of randomization for subjects who entered into the Maintenance part, or, for subjects who did not enter into the Maintenance part, before the treatment discontinuation date plus 28 days or any serious AE which occurred thereafter but was determined to be related to any study drug by the investigator. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild, Grade 2 = Moderate Grade, 3 = Severe Grade, 4 = Life threatening, Grade 5 = Death. Relation to study drug was determined by the investigator.
Time frame: Day 1 of Induction up to Week 23 (maximum treatment in Induction plus 4 weeks if not continuing into Maintenance)
Population: Safety population of participants treated during induction period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Serious TEAE | 177 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Treatment-related (trt-related) TEAE | 408 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-outcome of death | 32 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-study drug withdrawn | 35 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related serious TEAE | 82 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Severity Grade 3 or higher TEAE | 340 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-outcome of death | 7 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-study drug dose reduced or interrupted | 341 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-study drug withdrawn | 55 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Severity Grade 3/4 TEAE | 337 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-dose reduced or interrupted | 301 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE | 419 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-dose reduced or interrupted | 292 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-study drug withdrawn | 55 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-study drug withdrawn | 34 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-outcome of death | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-outcome of death | 7 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Severity Grade 3 or higher TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Treatment-related (trt-related) TEAE | 407 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Serious TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related serious TEAE | 80 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-study drug dose reduced or interrupted | 340 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Severity Grade 3/4 TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-outcome of death | 6 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Serious TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Severity Grade 3/4 TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Severity Grade 3 or higher TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Treatment-related (trt-related) TEAE | 394 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related serious TEAE | 73 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-study drug dose reduced or interrupted | 291 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-dose reduced or interrupted | 236 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | Trt-related TEAE-study drug withdrawn | 29 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-outcome of death | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period | TEAE-study drug withdrawn | 53 Participants |
Secondary
Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study
TEAE over entire study is defined as any adverse event (AE) with an onset on or after Day 1 of treatment for the Induction part, and before the treatment discontinuation date plus 28 days, or any serious AE which occurred thereafter but was determined to be related to any study drug by the investigator. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life threatening, Grade 5 = Death. Relation to study drug was determined by the investigator.
Time frame: From Day 1 up to 01 August 2019; (maximum treatment length plus 28 days); the maximum treatment duration was 234.1 weeks for entire study
Population: Safety population of participants randomized into maintenance, inclusive of both the induction and maintenance periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | 108 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 107 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 22 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 18 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 22 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | 109 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 115 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | 4 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | 54 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | 130 Participants |
| Nab-Paclitaxel + Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 129 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 18 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 113 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 22 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 22 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | NA Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 104 Participants |
| Best Supportive Care (BSC) | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 129 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 16 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 85 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 123 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 1 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 1 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 95 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | NA Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | NA Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 17 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | NA Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | NA Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 20 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 18 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 0 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 1 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 2 Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | NA Participants |
| Nab-Paclitaxel + BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | NA Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | 21 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | 62 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 52 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 45 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 0 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 1 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | 2 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | 48 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | 48 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 61 Participants |
| BSC: Induction + Maintenance | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 8 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 1 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 0 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | NA Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 8 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 52 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | NA Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | NA Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 45 Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | NA Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | NA Participants |
| BSC: TEAE Specific to Nab-Paclitaxel | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 61 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | NA Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | NA Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | NA Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 0 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | NA Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 1 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 37 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 7 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 58 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 45 Participants |
| BSC: TEAE Specific to Carboplatin | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | NA Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE | NA Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3/4 TEAE | NA Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-outcome of death | 0 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Treatment-related (trt-related) TEAE | 1 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related serious TEAE | 0 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug withdrawn | 0 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-study drug dose reduced or interrupted | 1 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Severity Grade 3 or higher TEAE | NA Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Serious TEAE | NA Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE- study drug withdrawn | 0 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | Trt-related TEAE-dose reduced or interrupted | 0 Participants |
| BSC: TEAE Specific to BSC | Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study | TEAE-outcome of death | NA Participants |
Secondary
Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) In Maintenance Beyond the Response in Induction
Overall response in the maintenance period was defined as the percentage of participants who showed an improvement in best overall response from stable disease (SD) or partial response (PR) during Induction to a Complete Response (CR) or PR during Maintenance according to RECIST 1.1 criteria and confirmed in no less than 28 days. Evaluation takes as reference the lesion measurement or status at the last tumor assessment before randomization to Maintenance. The 95% CI was calculated using Clopper-Pearson method. RECIST 1.1 Definition: - Complete response-disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. - Partial response-at least a 30% decrease in the sum of diameters of target lesions from baseline. - Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease.
Time frame: For the induction period the maximum treatment was 19 weeks for the maintenance period the maximum treatment was 150 weeks.
Population: Intent to treat population of participants randomized to the maintenance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) In Maintenance Beyond the Response in Induction | 9.6 percentage of participants |
| Best Supportive Care (BSC) | Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) In Maintenance Beyond the Response in Induction | 3.0 percentage of participants |
p-value: 0.097895% CI: [0.733, 13.574]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study
Overall response was defined as the percentage of participants with a confirmed assessment of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and confirmed in no less than 28 days. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. RECIST 1.1 Definition: - Complete response-disappearance of all target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to \< 10 mm. - Partial response-at least a 30% decrease in the sum of diameters of target lesions from baseline.
Time frame: Day 1 of treatment in the induction period and subsequent anticancer therapy, death or discontinuation up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study
Population: Intent to treat population of participants randomized to Maintenance
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study | 69.1 percentage of participants |
| Best Supportive Care (BSC) | Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study | 57.6 percentage of participants |
Comparison: 5% level of significance. The rate ratio and its 95% CI were based on the non-stratified analysis.p-value: 0.08795% CI: [0.948, 1.519]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study
Disease control rate was defined as the percentage of participants who had radiologic CR, PR or SD for \>= 6 weeks according to RECIST 1.1 criteria as determined by the investigator. Only participants with a confirmed CR/PR are included in this summary. Two timeframes are offered: - Time to confirmed response within the Induction timeframe. - Time to Confirmed Response Over the Entire Study, i.e. the time from Day 1 of treatment in Induction to the first occurrence of confirmed CR/PR any time during the study. RECIST 1.1 Definition: - CR- disappearance of all target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to \< 10 mm. - PR- at least a 30% decrease in the sum of diameters of target lesions from baseline; - SD- neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for PD. The 95% CI was calculated using Clopper-Pearson method.
Time frame: Induction is from Day 1 to a maximum treatment time of 19 weeks; entire study from Day 1 induction through maintenance up to PD; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study
Population: Induction includes the ITT population of participants treated during Induction. Entire Study includes the entire experience of the ITT population of participants randomized to maintenance.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study | 47.9 percentage of participants |
| Best Supportive Care (BSC) | Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study | 99.3 percentage of participants |
| BSC: Induction + Maintenance | Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study | 100.0 percentage of participants |
Comparison: The rate ratio and its 95% confidence interval are based on non-stratified analysis.95% CI: [0.978, 1.007]
Secondary
Time to Confirmed Response During Induction and Over the Entire Study
Time to confirmed complete or partial response (CR/PR) is defined as the time from day 1 of treatment in Induction to the first occurrence of confirmed CR/PR. Two timeframes are offered: - Time to confirmed response within the Induction timeframe. - Time to Confirmed Response Over the Entire Study, i.e. the time from Day 1 of treatment in Induction to the first occurrence of confirmed CR/PR any time during the study. Only participants with a confirmed CR or PR are included in this summary.
Time frame: Induction is from Day 1 to a maximum treatment time of 19 weeks; entire study from Day 1 Induction through Maintenance up to PD; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study
Population: Includes the ITT population of participants who had a response. Induction includes the ITT population of participants treated during Induction who had a response. Induction+Maintenance includes the ITT population of participants randomized to Maintenance who had a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-Paclitaxel + Best Supportive Care (BSC) | Time to Confirmed Response During Induction and Over the Entire Study | 1.446 months |
| Best Supportive Care (BSC) | Time to Confirmed Response During Induction and Over the Entire Study | 1.478 months |
| BSC: Induction + Maintenance | Time to Confirmed Response During Induction and Over the Entire Study | 1.413 months |