Roisné-Hamelin, Florian, Pobiega, Sabrina, Jézéquel, Kévin, Miron, Simona, Dépagne, Jordane, Veaute, Xavier, Busso, Didier, Du, Marie-Hélène Le, Callebaut, Isabelle, Charbonnier, Jean-Baptiste, Cuniasse, Philippe, Zinn-Justin, Sophie, Marcand, Stéphane, Park, Keunchil, Özgüroğlu, Mustafa, Vansteenkiste, Johan, Spigel, David, Yang, James C.H., Ishii, Hidenobu, Garassino, Marina, de Marinis, Filippo, Szczesna, Aleksandra, Polychronis, Andreas, Uslu, Ruchan, Krzakowski, Maciej, Lee, Jong-Seok, Calabrò, Luana, Arén Frontera, Osvaldo, Xiong, Huiling, Bajars, Marcis, Ruisi, Mary, Barlesi, Fabrice, Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Istanbul University Cerrahpasa, Department of Pulmonology, University Hospitals Leuven [Leuven], Sarah Cannon Research Institute [Nashville, Tennessee], National Taiwan University Cancer Center [Taipei], IRCCS Istituto Nazionale dei Tumori [Milano], Institut de Recherche Pierre Fabre, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Seoul National University Bundang Hospital (SNUBH), Azienda Ospedaliera Universitaria Senese, EMD Serono Research & Development Institute, Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Introduction: In the JAVELIN Lung 200 trial, avelumab (anti-programmed death-ligand 1 [PD-L1] antibody) did not significantly prolong overall survival (OS) versus docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report greater than 2-year follow-up data. Methods: Patients with stage IIIB or IV or recurrent NSCLC with disease progression after platinum-doublet chemotherapy were randomized 1:1 to avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m(2) every 3 weeks. The primary end point was OS in patients with PD-L1+ tumors (greater than or equal to 1% tumor cell expression; IHC 73-10 pharmDx assay). Results: Of 792 patients, 529 had PD-L1+ tumors (264 versus 265 in the avelumab versus docetaxel arms, respectively). As of March 4, 2019, median duration of follow-up for OS in the PD L1+ population was 35.4 months in the avelumab arm and 34.7 months in the docetaxel arm; study treatment was ongoing in 25 (9.5%) versus 0 patients, respectively. In the PD-L1+ population, 2-year OS rates (95% confidence interval [CI]) with avelumab versus docetaxel were 29.9% (24.5%-35.5%) versus 20.5% (15.6%-25.8%); in greater than or equal to 50% PD L1+ subgroups, 2-year OS rates were 36.4% (29.1%-43.7%) versus 17.7% (11.8%-24.7%) and in the greater than or equal to 80% subgroup were 40.2% (31.3%-49.0%) versus 20.3% (12.9%-28.8%), respectively. Median duration of response (investigator assessed) was 19.1 months (95% CI: 10.8-34.8) versus 5.7 months (95% CI: 4.1-8.3). Safety profiles for both arms were consistent with the primary analysis. Conclusions: Although the JAVELIN Lung 200 primary analysis (reported previously) revealed that avelumab did not significantly prolong OS versus docetaxel in patients with platinum-treated PD-L1+ NSCLC, posthoc analyses at 2 years of follow-up revealed that 2-year OS rates were doubled with avelumab in subgroups with higher PD-L1 expression (greater than or equal to 50% and greater than or equal to 80%). (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc., EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany; Pfizer; Merck KGaA, LL This study was sponsored by EMD Serono Research & Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer. Employees of the sponsor are coauthors of this manuscript and contributed to the design, execution, and interpretation of the analyses being reported, writing the report, and the decision to submit the article for publication, along with the other coauthors. The authors thank the patients and their families; the investigators, coinvestigators, and study teams at each participating center and at Merck KGaA, Darmstadt, Germany, and EMD Serono Research & Development Institute, Inc., Billerica, MA, an affiliate of Merck KGaA, Darmstadt, Germany, and Quintiles (Durham, NC) . Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking and funded by Merck KGaA and Pfizer.