TY - JOUR
T1 - Atezolizumab Versus Docetaxel in Pretreated Patients With NSCLC
T2 - Final Results From the Randomized Phase 2 POPLAR and Phase 3 OAK Clinical Trials
AU - Mazieres, Julien
AU - Rittmeyer, Achim
AU - Gadgeel, Shirish
AU - Hida, Toyoaki
AU - Gandara, David R.
AU - Cortinovis, Diego L.
AU - Barlesi, Fabrice
AU - Yu, Wei
AU - Matheny, Christina
AU - Ballinger, Marcus
AU - Park, Keunchil
N1 - Funding Information:
Disclosure: Dr. Mazieres reports receiving advisory board fees from Merck, Roche, AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Pfizer, Hengrui, Daiichi, Boehringer Ingelheim, and Pierre Fabre, and research grants from Roche , AstraZeneca , and Pierre Fabre . Dr. Rittmeyer reports receiving grants from AbbVie , AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Novartis , Pfizer , Roche / Genentech , and Boehringer Ingelheim outside of the submitted work. Dr. Gadgeel reports receiving grants from Genentech during the conduct of the study, and personal fees from Genentech, AstraZeneca, Daiichi Sankyo, Novartis, Novocure, Takeda, Xcovery, Boehringer Ingelheim, and Merck outside of the submitted work. Dr. Hida reports receiving grants and personal fees from Chugai Pharmaceutical Co. Ltd. during the conduct of the study, grants and personal fees from Ono Pharmaceutical, AstraZeneca, Novartis, Merck Sharp & Dohme, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Kissei, Taiho Pharmaceutical Co. Ltd., Pfizer, and Takeda Pharmaceutical Co. Ltd., and grants from Merck Bio, AbbVie , Daiichi Sankyo , Astellas , and Janssen Pharmaceutical outside of the submitted work. Dr. Gandara reports receiving grants from Roche / Genentech during the conduct of the study. Dr. Cortinovis reports receiving personal fees from Roche SpA, Bristol-Myers Squibb, AstraZeneca, Merck Sharp & Dohme, and Boehringer Ingelheim outside of the submitted work. Dr. Barlesi reports receiving personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, Merck Sharp & Dohme, Pierre Fabre, Pfizer, and Takeda outside of the submitted work. Drs. Yu, Matheny, and Ballinger report receiving grants from Genentech during the conduct of the study, personal fees from Genentech, and other fees from Roche outside of the submitted work. Dr. Park reports receiving other fees from Roche outside of the submitted work.
Funding Information:
This study was funded by F. Hoffmann-La Roche Ltd. and Genentech , Inc. The sponsors participated in the design of the studies, data collection and analysis, interpretation of results, and critical review of and contributions to the study reports. Support for third-party writing assistance, furnished by Denise Kenski, PhD, of Health Interactions, Inc., was provided by F. Hoffmann-La Roche Ltd. Dr. Ballinger contributed to conceptualization, investigation, data curation, writing—original draft, writing—review and editing, visualization, supervision, and project administration of the manuscript. Drs. Gadgeel and Barlesi contributed to investigation, resources, and writing—review and editing of the manuscript. Dr. Cortinovis contributed to investigation, writing—review and editing, and visualization of the manuscript. Dr. Gandara contributed to conceptualization, methodology, validation, investigation, writing—review and editing, visualization, supervision, and project administration of the manuscript. Dr. Hida contributed to resources, data curation, and writing—review and editing of the manuscript. Dr. Matheny contributed to conceptualization, data curation, writing—original draft, writing—review and editing, and project administration of the manuscript. Dr. Mazieres contributed to conceptualization, validation, investigation, resources, writing—original draft, writing—review and editing, visualization, and supervision of the manuscript. Dr. Park contributed to conceptualization, methodology, validation, investigation, resources, data curation, writing—original draft, writing—review and editing, and visualization of the manuscript. Dr. Rittmeyer contributed to conceptualization, investigation, resources, and writing—review and editing of the manuscript. Dr. Yu contributed to methodology, formal analysis, and writing—review and editing of the manuscript.
PY - 2020
Y1 - 2020
N2 - Introduction: The phase 2 POPLAR and phase 3 OAK studies of the anti–programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials. Methods: POPLAR randomized 287 patients (atezolizumab, 144; docetaxel, 143) and OAK randomized 1225 patients (atezolizumab, 613; docetaxel, 612). The patients received atezolizumab (1200 mg fixed dose) or docetaxel (75 mg/m2) every 3 weeks. Efficacy and safety outcomes were evaluated. Results: A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58–1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68–0.89). The 4-year OS rates in POPLAR were 14.8% (8.7–20.8) and 8.1% (3.2–13.0) and those in OAK were 15.5% (12.4–18.7) and 8.7% (6.2–11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively. Conclusions: Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies.
AB - Introduction: The phase 2 POPLAR and phase 3 OAK studies of the anti–programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials. Methods: POPLAR randomized 287 patients (atezolizumab, 144; docetaxel, 143) and OAK randomized 1225 patients (atezolizumab, 613; docetaxel, 612). The patients received atezolizumab (1200 mg fixed dose) or docetaxel (75 mg/m2) every 3 weeks. Efficacy and safety outcomes were evaluated. Results: A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58–1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68–0.89). The 4-year OS rates in POPLAR were 14.8% (8.7–20.8) and 8.1% (3.2–13.0) and those in OAK were 15.5% (12.4–18.7) and 8.7% (6.2–11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively. Conclusions: Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies.
KW - Atezolizumab
KW - Docetaxel
KW - Non–small cell lung cancer
KW - Overall survival
UR - http://www.scopus.com/inward/record.url?scp=85097040515&partnerID=8YFLogxK
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U2 - 10.1016/j.jtho.2020.09.022
DO - 10.1016/j.jtho.2020.09.022
M3 - Article
C2 - 33166718
AN - SCOPUS:85097040515
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
ER -