PMID- 35105689 OWN - NLM STAT- MEDLINE DCOM- 20220323 LR - 20220323 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 10 IP - 2 DP - 2022 Feb TI - Phase II study of atezolizumab with bevacizumab for non-squamous non-small cell lung cancer with high PD-L1 expression (@Be Study). LID - 10.1136/jitc-2021-004025 [doi] LID - e004025 AB - BACKGROUND: PD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models. METHODS: This single-arm phase II study investigated clinical benefits of adding bevacizumab 15 mg/kg to atezolizumab 1200 mg fixed dose in a first-line setting for advanced NS-NSCLC patients with PD-L1 expression >/=50% without EGFR/ALK/ROS1 alterations. Primary endpoint was objective response rate (ORR) assessed by central review committee. Secondary endpoints were progression-free survival (PFS), duration of response (DOR), OS, and safety. RESULTS: Of 39 enrolled patients, 33 (84.6%) had stage IV NSCLC and 36 (92.3%) had smoking history. As of March 31, 2020, no patient had a complete response and 25 patients had a partial response (ORR=64.1%, 95% CI 47.18 to 78.80). Twelve-month PFS and OS rates were 54.9% (35.65 to 70.60) and 70.6% (50.53 to 83.74), respectively. The median DOR in 25 responders was 10.4 months (4.63-not reached). The median treatment cycle was 12 (1 to 27). Nineteen patients discontinued study treatment because of disease progression (N=17) or immune-related adverse events (AEs) (N=2) (sclerosing cholangitis or encephalopathy). There were 23 serious AEs in 12 patients, but no grade 4/5 toxicity. CONCLUSIONS: Atezolizumab with bevacizumab is a potential treatment for NS-NSCLC with high PD-L1 expression. TRIAL REGISTRATION NUMBER: JapicCTI-184038. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. FAU - Seto, Takashi AU - Seto T AUID- ORCID: 0000-0002-2960-4364 AD - Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan setocruise@gmail.com. FAU - Nosaki, Kaname AU - Nosaki K AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Shimokawa, Mototsugu AU - Shimokawa M AD - Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan. FAU - Toyozawa, Ryo AU - Toyozawa R AD - Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. FAU - Sugawara, Shunichi AU - Sugawara S AD - Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan. FAU - Hayashi, Hidetoshi AU - Hayashi H AUID- ORCID: 0000-0001-8787-5587 AD - Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. FAU - Murakami, Haruyasu AU - Murakami H AD - Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. FAU - Kato, Terufumi AU - Kato T AUID- ORCID: 0000-0002-5853-1424 AD - Department of Respiratory Medicine, Kanagawa Cancer Center, Yokohama, Japan. FAU - Niho, Seiji AU - Niho S AD - Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Saka, Hideo AU - Saka H AD - Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center 4-1-1, Nagoya, Japan. FAU - Oki, Masahide AU - Oki M AD - Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center 4-1-1, Nagoya, Japan. FAU - Yoshioka, Hiroshige AU - Yoshioka H AD - Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan. FAU - Okamoto, Isamu AU - Okamoto I AD - Research Institute for Diseases of the Chest, Kyushu University Hospital, Fukuoka, Japan. FAU - Daga, Haruko AU - Daga H AD - Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan. FAU - Azuma, Koichi AU - Azuma K AD - Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University, Kurume, Japan. FAU - Tanaka, Hiroshi AU - Tanaka H AD - Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. FAU - Nishino, Kazumi AU - Nishino K AD - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. FAU - Tohnai, Rie AU - Tohnai R AD - Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan. FAU - Yamamoto, Nobuyuki AU - Yamamoto N AD - Internal Medicine III, Wakayama Medical University, Wakayama, Japan. FAU - Nakagawa, Kazuhiko AU - Nakagawa K AD - Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. LA - eng SI - JapicCTI/JapicCTI-184038 PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Immune Checkpoint Inhibitors) RN - 2S9ZZM9Q9V (Bevacizumab) RN - 52CMI0WC3Y (atezolizumab) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use MH - Bevacizumab/pharmacology/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Female MH - Humans MH - Immune Checkpoint Inhibitors/pharmacology/*therapeutic use MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged PMC - PMC8808447 OTO - NOTNLM OT - clinical trials OT - immunotherapy OT - lung neoplasms OT - phase II as topic COIS- Competing interests: TS reports grants and honoraria from Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, MSD, Novartis, Pfizer Japan, and Takeda Pharmaceutical; grants from Abbvie, Kissei Pharmaceutical, Loxo Oncology, and Merck Biopharma; honoraria from AstraZeneca, Bristol-Myers Squibb, Covidien Japan, Kyowa Kirin, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Taiho Pharmaceutical, and Thermo Fischer Scientific; and salary from Precision Medicine Asia outside the submitted work. KNosaki reports personal fees from Chugai Pharmaceutical outside the submitted work. RToyozawa reports honoraria from Bristol-Myers Squibb, Chugai Pharmaceutical, Kyowa Kirin, MSD, Nippon Boehringer Ingelheim, Nippon Kayaku, and Taiho Pharmaceutical; grants from Abbvie, Amgen, Daiichi Sankyo, Pfizer Japan, and Takeda Pharmaceutical; and grants and honoraria from Eli Lilly Japan, and Novartis outside the submitted work. SS reports lecture fees from Chugai Pharmaceutical, AstraZeneca, MSD, Bristol-Myers Squibb, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, Novartis, Kyowa Kirin, and Yakult Honsha outside the submitted work. HH reports grants and personal fees from Chugai Pharmaceutical during the conduct of the study; grants and personal fees from AstraZeneca, Nippon Boehringer Ingelheim, and Ono Pharmaceutical; personal fees from Bristol-Myers Squibb, Eli Lilly Japan, Kyorin Pharmaceutical, Merck Biopharma, MSD, Novartis, Pfizer Japan, Shanghai Haihe Biopharma, Taiho Pharmaceutical, and Takeda Pharmaceutical; and grants from Chugai Pharmaceutical outside the submitted work. HM reports grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Takeda Pharmaceutical, and Daiichi Sankyo; grants from Abbvie and IQVIA; and personal fees from Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Pfizer, Novartis, Eli Lilly Japan, and Taiho Pharmaceutical outside the submitted work. TK reports grants and fees for speaking/advisory board/supported research from Abbvie, Amgen, AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Merck Biopharma, MSD, and Novartis; grants, speaker fees, and supported research from Bristol-Myers Squibb; grants and fees for speaking/scientific advice/supported research from Ono Pharmaceutical, Pfizer, and Taiho Pharmaceutical; speaker fees from Boehringer Ingelheim; fees for speaking/advisory boards from Daiichi Sankyo; fees for advisory board from Nippon Kayaku; fees for scientific advice from Takeda Pharmaceutical; and grants from Regeneron Pharmaceuticals outside the submitted work. SN reports grants and personal fees from Chugai Pharmaceutical during the conduct of the study; and grants and personal fees from AstraZeneca, Pfizer, Taiho Pharmaceutical, Boehringer Ingelheim, MSD, Ono Pharmaceutical, Kyorin Pharmaceutical, and Eli Lilly Japan; personal fees from Janssen Pharmaceutical and Novartis; and grants from Merck Serono, Sanofi, Shionogi, Takeda Pharmaceutical, and Teijin Pharma outside the submitted work. HY reports honoraria for lecture fees from Chugai Pharmaceutical during the conduct of the study; and honoraria for lecture fees from AstraZeneca, Nippon Boehringer Ingelheim, Bristol-Myers Squibb, Taiho Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Kyowa Kirin, MSD, Delta-Fly Pharma, Pfizer, Novartis, and Nippon Kayaku outside the submitted work. IO reports grants from Taiho Pharmaceutical during the conduct of the study; and grants and personal fees from AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, Bristol-Myers Squibb, and Chugai Pharmaceutical; grants from Astellas Pharma, Novartis, and Abbvie; and personal fees from Pfizer outside the submitted work.HD reports personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Pfizer, and Ono Pharmaceutical outside the submitted work. KA reports personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, MSD Oncology, and Bristol-Myers Squibb outside the submitted work. HT reports grants from Chugai Pharmaceutical during the conduct of the study; grants and personal fees from Bristol-Myers Squibb, Eli Lilly, MSD, Taiho Pharmaceutical, Pfizer, Novartis, Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Merck, and Ono Pharmaceutical outside the submitted work. KNishino reports grants and personal fees from Nippon Boehringer Ingelheim and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Roche Diagnostics, Novartis, Pfizer, Ono Pharmaceutical, and Merck outside the submitted work. RTohnai reports research expenses from Chugai Pharmaceutical during the conduct of the study. NY reports grants and personal fees from Chugai Pharmaceutical during the conduct of the study; and grants and personal fees from MSD, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceutical, Eli Lilly Japan, Boehringer Ingelheim, Novartis, and Pfizer; personal fees from Thermo Fisher Scientific, Bristol-Myers Squibb, Life Technologies Japan, Nippon Kayaku, and Merck Biopharma; and grants from Astellas Pharma, Tsumura, Shionogi, Abbvie, Amgen, Kyorin Pharmaceutical, Eisai, Terumo Corporation, Toppan Printing, and Tosoh Corporation outside the submitted work. KNakagawa reports grants and personal fees from AstraZeneca, MSD, Nippon Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, and Merck Serono/Merck Biopharma, and grants, personal fees and other consulting and advisory role fees from Astellas Pharma, Ono Pharmaceutical, Pfizer, and Eli Lilly Japan during the conduct of the study; personal fees from Medicus Shuppan Publishers, CareNet, Medical Review, Roche Diagnostics, Medical Mobile Communications, 3H Clinical Trial, Nichi-Iko Pharmaceutical, Yodosha, Nikkei Business Publications, Thermo Fisher Scientific, Yomiuri Telecasting Corporation, Nippon Kayaku, Hisamitsu Pharmaceutical, Nanzando, and Amgen; personal fees and others from Kyorin Pharmaceutical; grant, personal fees and other consulting/advisor role fees from Takeda Pharmaceutical; grants and personal fees from Taiho Pharmaceutical, Abbvie, Kyowa Kirin, and Bayer Yakuhin; and grants from SymBio Pharmaceuticals, Icon Japan, PAREXEL International, Kissei Pharmaceutical, EPS Corporation, Syneos Health, Pfizer R&D Japan, A2 Healthcare, IQVIA, Eisai, CMIC Shift Zero, EPS International, Otsuka Pharmaceutical, PRA Health Sciences, Covance Japan, Medical Research Support, Sanofi, PPD-SNBL, Japan Clinical Research Operations, Sysmex Corporation, Mochida Pharmaceutical, and GlaxoSmithKline outside the submitted work. All other authors declare no competing interests. EDAT- 2022/02/03 06:00 MHDA- 2022/03/24 06:00 PMCR- 2022/02/01 CRDT- 2022/02/02 05:32 PHST- 2022/01/11 00:00 [accepted] PHST- 2022/02/02 05:32 [entrez] PHST- 2022/02/03 06:00 [pubmed] PHST- 2022/03/24 06:00 [medline] PHST- 2022/02/01 00:00 [pmc-release] AID - jitc-2021-004025 [pii] AID - 10.1136/jitc-2021-004025 [doi] PST - ppublish SO - J Immunother Cancer. 2022 Feb;10(2):e004025. doi: 10.1136/jitc-2021-004025.