A Study of Atezolizumab in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin+Nab-Paclitaxel in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Carcinoma, Non-Squamous Non-Small Cell Lung Clinical Trial

— IMpower130  

Official title:

A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02367781
• Other study ID #: GO29537
• Secondary ID: 2014-003206-32
• Status: Completed
• Phase: Phase 3
• Start date: April 16, 2015
• Est. completion date: January 18, 2021

Study information

• Verified date: July 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab (an engineered anti-programmed death-ligand 1 [PD-L1] antibody) in combination with carboplatin+nab-paclitaxel compared with treatment with carboplatin+nab-paclitaxel in chemotherapy-naive participants with Stage IV non-squamous NSCLC. Participants were randomized in a 2:1 ratio to Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin) or Arm B (Nab-Paclitaxel+Carboplatin).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 723
• Est. completion date: January 18, 2021
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group performance status of 0 or 1

• Histologically or cytologically confirmed, Stage IV non-squamous NSCLC

• Participants with no prior treatment for Stage IV non-squamous NSCLC

• Previously obtained archival tumor tissue or tissue obtained from fresh biopsy at screening

• Measurable disease, as defined by RECIST v1.1

• Adequate hematologic and end organ function

Exclusion Criteria:

Cancer-Specific Exclusions:

• Active or untreated central nervous system metastases

• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome

General Medical Exclusions:

• Pregnant or lactating women

• History of autoimmune disease

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

• Positive test for human immunodeficiency virus

• Active hepatitis B or hepatitis C

• Severe infection within 4 weeks prior to randomization

• Significant cardiovascular disease

• Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures

Exclusion Criteria Related to Medications:

• Prior treatment with cluster of differentiation 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1, and anti-PD-L1 therapeutic antibodies

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Non-Squamous Non-Small Cell Lung

Intervention

Drug:
• Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab was administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Atezolizumab was administered to participants who were randomized to "Arm A (Atezolizumab + Nab-Paclitaxel + Carboplatin)" and to participants in "Arm B (Nab-Paclitaxel + Carboplatin)" who cross over at progression.
• Carboplatin
Carboplatin was administered at area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle.
• Nab-Paclitaxel
Nab-paclitaxel was administered as IV infusion at a dose of 100 milligrams per square meter (mg/m^2) on Days 1, 8, and 15 of each 21-day cycle.
• Pemetrexed
Switch maintenance to pemetrexed can be administered within 6 weeks of Day 1 of the last induction cycle.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	CHU Ambroise Paré	Mons
Belgium	Werken Glorieux VZW	Ronse
Belgium	GasthuisZusters Antwerpen	Wilrijk
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	William Osler Health Centre	Etobicoke	Ontario
Canada	Cite de La Sante de Laval; Hemato-Oncologie	Laval	Quebec
Canada	Hôpital Maisonneuve - Rosemont	Montreal	Quebec
Canada	BC Cancer - Surrey	Surrey	British Columbia
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Institut Hospitalier Franco-Britannique; Cancerologie	Levallois-Perret
France	Fondation Hopital Saint Joseph;Cardiologie Clinique	Marseille
France	Clinique Clementville; Hopital De Jour	Montpellier
France	Centre D'oncologie de Gentilly; Service Oncologie Medicale	Nancy
France	Clinique Catherine de Sienne	Nantes
France	Hopital American de Paris (American Hospital of Paris)	Neuilly sur Seine
France	HOPITAL DE LA SOURCE; Service de Cardiologie, Point Jaune	Orleans
France	Hopital Pontchaillou	Rennes
France	Centre Hospitalier Regional Sud Reunion; Service de Pneumologie	Saint Pierre
France	Hopital d'Instruction des Armees de Begin	Saint-Mande
France	CHRU Nancy; Pneumologie	Vandoeuvre-lès-nancy
Germany	Charite - Universitätsmedizin Berlin; Klinik fur Infektiologie und Pneumologie	Berlin
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Bezirksklinikum Obermain	Ebensfeld
Germany	Helios Klinikum Erfurt	Erfurt
Germany	St. Antonius Hospital	Eschweiler
Germany	Klinikum Esslingen GmbH; Frauenklinik	Esslingen Am Neckar
Germany	Malteser Krankenhaus St. Franziskus-Hospital	Flensburg
Germany	Krankenhaus Nordwest	Frankfurt am Main
Germany	Asklepios Fachkliniken GmbH	Gauting
Germany	SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie	Gera
Germany	Robert Bosch Krankenhaus; Pneumologie und pneumologische Onkologie	Gerlingen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Germany	St. Vincentius Kliniken Karlsruhe	Karlsruhe
Germany	Klinikum Kassel; Hautklinik	Kassel
Germany	Katholisches Klinikum Marienhof	Koblenz Am Rhein
Germany	Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I	Lubeck
Germany	Klinikum Mannheim GmbH Universitätsklinikum	Mannheim
Germany	Johannes Wesling Klinikum Minden	Minden
Germany	LMU Klinikum der Universitat Munchen	Munchen
Germany	Universitätsklinikum Tübingen	Tuebingen
Germany	Praxis fur Haematologie und Internistische Onkologie	Velbert
Germany	Schwarzwald-Baar Klinikum/VS GmbH; Onkologie/Hämatologie/Infektologie	Villingen-Schwenningen
Germany	Helios Klinik Wuppertal	Wuppertal
Israel	Soroka University Medical Centre	Beer Sheva
Israel	Assaf Harofeh Medical Center	Beer Yaakov
Israel	Hadassah Ein Karem Hospital; Oncology Dept	Jerusalem
Israel	Meir Medical Center; Oncology	Kfar-Saba
Israel	Galilee Medical Center	Nahariya
Israel	Rabin Medical Center	Petach Tiqwa
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Rambam Health Corporation; Oncology Institute	Rambam
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Ctr; Oncology	Tel Aviv
Italy	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati	Avellino	Campania
Italy	Ospedale Clinicizzato SS Annunziata	Chieti	Abruzzo
Italy	Ospedale Di Macerata; Oncologia	Macerata	Marche
Italy	Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica	Napoli	Campania
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Ospedale Santa Maria Della; Misericordia Di Perugia; Farmacia Ospedaliera	Perugia	Umbria
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	LA Coruña
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital de San Pedro de Alcantara	Caceres
Spain	Consorcio Hospitalario Provincial de Castellon	Castellon DE LA Plana/castello DE LA Plana	Castellon
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Complejo Hospitalario de Jaen	Jaen
Spain	Hospital Son Llatzer	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario de Canarias	S. Cristobal De La Laguna	Tenerife
Spain	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital NisA 9 de Octubre	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
United States	University Cancer & Blood Center, LLC; Research	Athens	Georgia
United States	Center For Cancer and Blood Disorders	Bethesda	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital	Carrollton	Georgia
United States	Presbyterian Hospital	Charlotte	North Carolina
United States	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	University Oncology Associates	Chattanooga	Tennessee
United States	University of Illinois at Chicago	Chicago	Illinois
United States	The Christ Hospital	Cincinnati	Ohio
United States	Mark H. Zangmeister Center	Columbus	Ohio
United States	University of Miami School of Medicine - Sylvester at Deerfield	Deerfield Beach	Florida
United States	SCRI The Center For Cancer and Blood Disorders	Denton	Texas
United States	Duke University Medical Center; Department of Medicine	Durham	North Carolina
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Southcoast Health System	Fairhaven	Massachusetts
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	Fort Wayne Med Oncology & Hematology Inc	Fort Wayne	Indiana
United States	Banner MD Anderson Cancer Center	Greeley	Colorado
United States	Greenville Health System; Cancer Center	Greenville	South Carolina
United States	Oncology Hematology Care, Inc.	Hamilton	Ohio
United States	Pinnacle Health	Harrisburg	Pennsylvania
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Joliet Oncology-Hematology; Associates, Ltd.	Joliet	Illinois
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Suburban Hematology / Oncology Associates	Lawrenceville	Georgia
United States	Lahey Clinic Med Ctr	Lexington	Kentucky
United States	Southeast Nebraska Cancer Ctr	Lincoln	Nebraska
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Cancer Inst. of New Jersey	New Brunswick	New Jersey
United States	Laura and ISAAC Perlmutter Cancer Center at NYU Langone.	New York	New York
United States	Southeastern Regional Medical Center, Inc.	Newnan	Georgia
United States	Eastern Connecticut Hematology and Oncology Associates; (ECHO)	Norwich	Connecticut
United States	Kaiser Permanente Oakland Medical Center	Oakland	California
United States	Florida Hospital	Orlando	Florida
United States	Illinois Cancer Care	Peoria	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Quincy Medical Group	Quincy	Illinois
United States	Va Sierra Nevada Health Care System	Reno	Nevada
United States	Mayo Clinic	Rochester	Minnesota
United States	Kaiser Permanente Medical Center - Roseville	Roseville	California
United States	Kaiser Permanente - Sacramento Medical Center and Medical Offices	Sacramento	California
United States	Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)	Saint Petersburg	Florida
United States	W.G. Bill Hefner VA Medical Center	Salisbury	North Carolina
United States	Cancer Care Network of South Texas - SAT & BC	San Antonio	Texas
United States	Kaiser Permanente - San Francisco Medical Center	San Francisco	California
United States	Kaiser Permanente - San Jose Medical Center	San Jose	California
United States	Kaiser Permanente - San Leandro Medical Center	San Leandro	California
United States	Kaiser Permanente - Santa Clara	Santa Clara	California
United States	Kaiser Permanente - South San Francisco	South San Francisco	California
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Southern Illinois University, Simmons Cancer Institute	Springfield	Illinois
United States	Hematology and Oncology Associates at Bridgepoint	Tupelo	Mississippi
United States	Kaiser Permanente; Oncology Clinical Trials	Vallejo	California
United States	Kaiser Permanente - Walnut Creek	Walnut Creek	California
United States	SCRI Florida Cancer Specialists East	West Palm Beach	Florida
United States	Clinical Research Alliance	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population	PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first in the ITT-WT population.	Up to approximately 35 months after first patient enrolled
Primary	Overall Survival (OS) in the ITT-WT Population	OS is defined as the time between the date of randomization and date of death from any cause in the ITT-WT population.	Up to approximately 35 months after first patient enrolled
Secondary	PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population	PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. The ITT population was defined as all randomized participants, regardless of receipt of the assigned treatment. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. The PD-L1 expression WT population is defined as the PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation.	Up to approximately 35 months after first subject enrolled
Secondary	OS as Determined by the Investigator Using Recist v1.1 in the ITT Population	OS is defined as the time between the date of randomization and date of death from any cause in the ITT population.	Up to approximately 41 months after first subject enrolled
Secondary	OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population	OS is defined as the time between the date of randomization and date of death from any cause in the PD-L1 Expression Population and PD-L1 Expression WT Population. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. The PD-L1 expression WT population is defined as the PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation.	Up to approximately 35 months after first patient enrolled
Secondary	Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT-WT Population	ORR (confirmation not required) is defined as the proportion of participants with an objective response, either CR or PR, with the use of RECIST v1.1, as determined by the investigator in the ITT-WT population.	Up to approximately 41 months after first subject enrolled
Secondary	Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population	ORR (confirmation not required) is defined as proportion of participants with an objective response, either CR or PR, with the use of RECIST v1.1, as determined by investigator in ITT population, PD-L1 Expression population, and PD-L1 Expression WT population. ITT population was defined as all randomized participants, regardless of receipt of the assigned treatment. PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. PD-L1 expression WT population is defined as PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation.	Up to approximately 35 months after first subject enrolled
Secondary	Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 in ITT-WT Population, ITT Population, and PD-L1 Expression Population and PD-L1 Expression WT Population	DOR,defined for participants with objective response (OR) as time from 1st documented OR to documented disease progression as determined by investigator using RECIST v1.1,or death from any cause,whichever occurs 1st.ITT defined as all randomized participants,regardless of receipt of assigned treatment.ITT-WT defined as ITT population excluding participants with activating EGFR mutation or ALK translocation.PD-L1 expression population is defined as one of following:PD-L1 IHC TC1/2/3 or IC1/2/3 population,defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue;PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue;PD-L1 IHC TC3 or IC3 population,defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue.PD-L1 expression WT is defined as PD-L1 expression population excluding participants with activating EGFR mutation or ALK translocation.	Up to approximately 35 months after first subject enrolled
Secondary	Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population	The OS rate at the 1- and 2-year landmark time points after randomization.	Up to 41 months after first patient enrolled, years 1 and 2 reported
Secondary	Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population	The OS rate at the 1- and 2-year landmark time points after randomization in the PD-L1 Expression Population and PD-L1 Expression WT Population. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. The PD-L1 expression WT population is defined as the PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation.	Up to 35 months after first patient enrolled, years 1 and 2 reported
Secondary	Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population	Defined as time from randomization to confirmed deterioration (10-point change) on the combined European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core (EORTC QLQ-C30) and supplemental lung cancer module (EORTC QLQ-LC13) symptom subscales.	Up to approximately 35 months after first subject enrolled
Secondary	Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale	Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of =0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of=0.5 points for chest pain score is considered to be clinically significant.	Up to approximately 35 months after first subject enrolled
Secondary	Percentage of Participants With Adverse Events	Percentage of participants with at least one adverse event. Adverse event onset date before cross over.	Up to approximately 69 months after first patient enrolled
Secondary	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab	Baseline prevalence and post-baseline incidence of anti-drug antibodies (ADA) to Atezolizumab in the Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) and Arm B Carboplatin+nab-paclitaxel Crossover Participants	Up to approximately 35 months after first subject enrolled
Secondary	Maximum Observed Serum Concentration (Cmax) of Atezolizumab for Patients in Atezolizumab+Carboplatin+Nab-Paclitaxel Arm	Predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.	Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days)
Secondary	Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Atezolizumab+Carboplain+Nab-Paclitaxel	Predose samples will be collected on the same day of treatment administration.	Cycle 1 Day 21, Cycle 2 Day 21, Cycle 3 Day 21, and Cycle 7 Day 21 (Cycle length = 21 days)
Secondary	Plasma Concentrations of Carboplatin		Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 hour after carboplatin infusion (infusion duration=15 to 30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months)
Secondary	Plasma Concentrations of Nab-Paclitaxel Reported as Total Paclitaxel		Predose (same day of treatment administration), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after nab-paclitaxel infusion (infusion duration=30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months)