Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Antiemetics

Gastrointestinal Agents

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Taxane

Tubulin Modulators

Antimitotic Agents

Dosing will occur in two phases - induction and maintenance. During induction, the subject will receive Abraxane plus carboplatin as standard of care. At the end of 4 cycles, if the subject has a complete response, partial response, or stable disease, he/she will continue on to the maintenance phase. Maintenance dosing on this arm includes Abraxane plus best supportive care.

Dosing will occur in two phases - induction and maintenance. During induction, the subject will receive Abraxane plus carboplatin as standard of care. At the end of 4 cycles, if the subject has a complete response, partial response, or stable disease, he/she will continue on to the maintenance phase. Maintenance dosing on this arm includes best supportive care only.

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

Abraxane (Induction)

6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion

Carboplatin (Induction)

100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, administered as standard of care

Abraxane (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

Best Supportive Care (Maintenance)

6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion, administered as standard of care

Teng Jin Ong, MD

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.

The sponsor used 15 Sep 2017 as the database cut-off date.

Safety and Efficacy Study of Abraxane as Maintenance Treatment After Abraxane Plus Carboplatin in 1st Line Stage IIIB / IV Squamous Cell Non-small Cell Lung Cancer

A Phase III, Randomized, Open-Label, Multi-Center, Safety and Efficacy Study to Evaluate Nab-Paclitaxel (Abraxane®) as Maintenance Treatment After Induction With Nab-Paclitaxel Plus Carboplatin in Subjects With Squamous Cell Non-Small Cell Lung Cancer (NSCLC)

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

Celgene

All-Cause Mortality events are reported from the ITT population (participants who received at least 1 dose of study treatment regardless of whether they had efficacy assessments collected); up to date of 01 August 2019.

During induction, participants received nab-paclitaxel plus carboplatin as standard of care: nab-paclitaxel 100 mg/m\^2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle and carboplatin AUC = 6 mg\*min/mL IV on Day 1 of each 21-day cycle. If the participant had radiological or clinical progressive disease (PD), they were discontinued from the study and not followed. If the participant had a complete response, partial response, or stable disease without PD at the end of 4 cycles, he/she were eligible to be randomised to the maintenance phase

All Participants - Induction

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.

Nab-Paclitaxel + Best Supportive Care (Maintenance)

Maintenance Phase: Following randomization, participants in this treatment arm were administered best supportive care (only) until disease progression.

Nab-Paclitaxel + Best Supportive Care (BSC)

Best Supportive Care (BSC)

Total

Continuous age values in Total column represent the 202 participants in the Maintenance Period. Induction includes participants who were enrolled and treated however, baseline characteristics for non-randomised participants is not displayed. The total number represents the ITT population in the maintenance phase.

Age, Continuous

<65 years

>=65 years

<70 years

>=70 years

<75 years

>=75 years

Induction includes participants who were enrolled and treated in the induction phase. Baseline characteristics are displayed only for participants randomised in the maintenance phase. The total number represents the ITT population in the maintenance phase.

Age, Customized

Sex: Female, Male

Induction includes participants who were enrolled and treated in the induction phase. Baseline characteristics are displayed only for participants randomized in the maintenance phase. The total number represents the ITT population in the maintenance phase.

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

ECOG PS assesses how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. - 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled. Baseline characteristics are displayed only for participants randomized in the maintenance phase. The total number represents the ITT population in the maintenance phase.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Tumor response to Induction part chemotherapy for stratification is the response assessed at the last computed tomography (CT) scan before randomization. Baseline characteristics are displayed only for participants randomized in the maintenance phase. The total number represents the ITT population in the maintenance phase.

Overall Tumor Response at End of Induction

The histology categories included those with a tumor histology of squamous versus non-squamous types. Baseline characteristics for non-randomized participants is not displayed. The total number represents the ITT population in the maintenance phase.

Confirmed Histology

Disease stage = how big the tumor is and how far it has spread. Disease stages range from 0 (not spread) to IV (spread throughout the body). Stage 0: the cancer has not spread beyond the inner lining of the lung. Stage I: the cancer is small and hasn't spread to the lymph nodes (LN). Stage II: the cancer has spread to some LN near the original tumor. Stage III: the cancer has spread to nearby tissue or spread to far away LN. Stage IV: the cancer has spread to other organs such as lung, brain, or liver. BLC are displayed for participants randomized in the maintenance phase.

Disease Stage at Enrollment

Induction includes participants who were enrolled and treated however, baseline characteristics (BLC) for non-randomised participants is not displayed. The total number represents the ITT population in the maintenance phase.

Anne McClain, Senior Manager

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.

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.

Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance

Intent to Treat population of participants randomized to maintenance.

Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance

5% level of significance. The rate ratio and its 95% CI were based on the non-stratified analysis.

Participants randomized to this treatment arm for Maintenance, inclusive of their experience during Induction. During induction, participants received nab-paclitaxel plus carboplatin as standard of care: nab-paclitaxel 100 mg/m\^2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle and carboplatin AUC = 6 mg\*min/mL IV on Day 1 of each 21-day cycle. If the participant had a complete response, partial response, or stable disease without PD at the end of 4 cycles, he/she continued to the maintenance phase. Maintenance: 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.

Nab-Paclitaxel + BSC: Induction + Maintenance

Participants randomized to this treatment arm for Maintenance, inclusive of their experience during Induction. During induction, participants received nab-paclitaxel plus carboplatin as standard of care: nab-paclitaxel 100 mg/m\^2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle and carboplatin AUC = 6 mg\*min/mL IV on Day 1 of each 21-day cycle. If the participant had a complete response, partial response, or stable disease without PD at the end of 4 cycles, he/she continued to the maintenance phase. Maintenance: Following randomization, participants in this treatment arm were administered best supportive care (only) until disease progression.

BSC: Induction + Maintenance

Intent to treat population of participants randomized to Maintenance

Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study

Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study

ITT population of participants randomized to Maintenance.

Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study

Intent to treat population of participants randomized to the maintenance period.

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

The rate ratio and its 95% confidence interval are based on non-stratified analysis.

Participants randomized to this treatment arm for Maintenance, inclusive of their experience during Induction. During induction, During induction, participants received nab-paclitaxel plus carboplatin as standard of care: nab-paclitaxel 100 mg/m\^2 IV infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle and carboplatin AUC = 6 mg\*min/mL IV on Day 1 of each 21-day cycle. If the participant had a complete response, partial response, or stable disease without PD at the end of 4 cycles, he/she continued to the maintenance phase. Maintenance: 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.

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.

Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study

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.

Time to Confirmed Response During Induction and Over the Entire Study

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.

The ITT population of participants randomized to the maintenance period and had a confirmed partial or complete response.

Kaplan-Meier Estimate for Duration of Response Over the Entire Study

TEAE

Serious TEAE

Severity Grade 3/4 TEAE

Severity Grade 3 or higher TEAE

Treatment-related (trt-related) TEAE

Trt-related serious TEAE

TEAE-study drug dose reduced or interrupted

Trt-related TEAE-dose reduced or interrupted

TEAE-study drug withdrawn

Trt-related TEAE-study drug withdrawn

TEAE-outcome of death

Trt-related TEAE-outcome of death

TEAE categories specific to nab-paclitaxel intervention as determined by the investigator.

TEAE Specific to Nab-Paclitaxel

TEAE categories specific to carboplatin intervention as determined by the investigator.

TEAE Specific to Carboplatin

Safety population of participants treated during induction period.

Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period

Trt-related TEAE- study drug withdrawn

Participants randomized to this treatment arm for Maintenance, inclusive of their experience during Induction. During induction, participants received nab-paclitaxel plus carboplatin as standard of care. If the participant had a complete response, partial response, or stable disease without PD at the end of 4 cycles, he/she continued to the maintenance phase. Maintenance: 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.

TEAE categories specific to nab-paclitaxel intervention, as determined by the investigator, for participants randomized to the Nab-Paclitaxel + BSC treatment arm. Nab-paclitaxel was administered during Induction and Maintenance.

Nab-Paclitaxel + BSC: TEAE Specific to Nab-Paclitaxel

TEAE categories specific to carboplatin intervention as determined by the investigator, for participants randomized to the Nab-Paclitaxel + BSC treatment arm. Carboplatin was administered during Induction.

Nab-Paclitaxel + BSC: TEAE Specific to Carboplatin

TEAE categories specific to best supportive care (BSC) as determined by the investigator, for participants randomized to the Nab-Paclitaxel + BSC treatment arm. BSC was administered during Maintenance.

Nab-Paclitaxel + BSC: TEAE Specific to BSC

Participants randomized to this treatment arm for Maintenance, inclusive of their experience during Induction. During induction, participants received nab-paclitaxel plus carboplatin as standard of care. If the participant had a complete response, partial response, or stable disease without PD at the end of 4 cycles, he/she continued to the maintenance phase. Maintenance: Following randomization, participants in this treatment arm were administered best supportive care (only) until disease progression.

TEAE categories specific to nab-paclitaxel intervention, as determined by the investigator, for participants randomized to the BSC treatment arm. Nab-paclitaxel was administered during Induction.

BSC: TEAE Specific to Nab-Paclitaxel

TEAE categories specific to carboplatin intervention as determined by the investigator, for participants randomized to the BSC treatment arm. Carboplatin was administered during Induction.

BSC: TEAE Specific to Carboplatin

TEAE categories specific to best supportive care (BSC) as determined by the investigator, for participants randomized to the BSC treatment arm. BSC was administered during Maintenance.

BSC: TEAE Specific to BSC

Safety population of participants randomized into maintenance, inclusive of both the induction and maintenance periods.

Spots Global Cancer Trial Database for best supportive care (maintenance)