Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer

Abstract

Background: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous non-small-cell lung cancer (NSCLC).

Patients and methods: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC).

Results: Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively.

Conclusion: The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.

Keywords: NSCLC; bevacizumab; nivolumab.

Conflict of interest statement

Disclosure SS reports a grant from Ono and personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Kyowa Hakko Kirin, MSD, Nippon Boehringer Ingelheim, Novartis, ONO, Pfizer, and Taiho. J-SL, J-HK, HRK, and KHL report a grant from Ono. NI reports grants from Chugai, Daiichi Sankyo, Eli Lilly, MSD KK, Nippon Boehringer Ingelheim, Novartis, and Taiho; personal fees from AstraZeneca, Chugai, Eli Lilly, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, and Taiho. TH reports grants from AbbVie, Astellas, AstraZeneca, Bristol-Meyers Squibb, Chugai, Daiichi Sankyo, Eisai, Ignyta, Janssen, Kissei, Merck Serono, MSD, Nippon Boehringer Ingelheim, Novartis, ONO, Pfizer, Taiho, and Takeda; personal fees from AstraZeneca, Bristol-Meyers Squibb, Chugai, Kissei, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, Pfizer, Taiho, and Takeda. TY reports grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, MSD, Ono, and Takeda; personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, and Novartis. HT reports grants from Astra Zeneca, Boehringer Ingelheim, Chugai, Eli Lilly, MSD, Ono, and Taiho; personal fees from Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lilly, MSD, Novartis, Ono, Pfizer, and Taiho. C-TY reports personal fees from Boehringer Ingelheim, Chugai, MSD, Ono, Pfizer, and Roche. MN reports grants from AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Novartis, ONO, Pfizer, Taiho, and Takeda; personal fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Merck Biopharma, MSD, Novartis, ONO, Pfizer, Taiho, Takeda, and TEIJIN. YO reports grants from AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Ignyta, Janssen, Kyorin, Kyowa Hakko Kirin, MSD, Nippon Kayaku, Novartis, Ono, Taiho, and Takeda; personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Chugai, Eli Lilly, Janssen, Kyorin, MSD, Nippon Kayaku, Novartis, Ono, Pfizer, Taiho, and Takeda. TT reports grant from Ono and personal fees from Chugai and Lilly. NY reports grants from Astellas, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Ono, Pfizer, Shionogi, Taiho, Terumo, Toppan Printing, Tosoh, and Tsumura; personal fees from Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly Japan, MSD, Nippon Kayaku, Novartis, Ono, Pfizer, Taiho, Takeda, and Thermo Fisher Scientific. C-JY reports other support from Ono. HA reports grants from Chugai and MSD; personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai, MSD, and Ono. YN and NS are employees of Ono. KN reports grants from A2 Healthcare, AbbVie, Astellas, AstraZeneca, Bayer Yakuhin, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, CMIC Shift Zero, Eisai, Eli Lilly, EP-CRSU, EPS, EPS International, GRITSONE ONCOLOGY, ICON Japan, inVentiv Health, Kissei, Kyowa Hakko Kirin, Linical, Merck Serono/Merck Biopharma, MSD, Nippon Boehringer Ingelheim, Novartis, Ono, Otsuka, PAREXEL International, Pfizer, Pfizer R&D Japan, Quintiles/IQVIA Services JAPAN, Symbio, Syneos Health, Taiho, and Takeda; personal fees from 3H Clinical Trial, AbbVie, Astellas, AstraZeneca, Bayer Yakuhin, Bristol-Myers Squibb, Care Net, Chugai, Clinical Trial, Daiichi Sankyo, Eli KYORIN, Lilly, Medical Mobile Communications, Medical Review, MEDICUS SHUPPAN Publishers, Merck Serono/Merck Biopharma, MSD, NANZANDO, Nichi-Iko, Nikkei Business Publications, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Ono, Pfizer, Reno. Medical, Roche Diagnostics, Symbio, Taiho, Takeda, Thermo Fisher Scientific, YODOSHA, and YOMIURI TELECASTING; other supports from Eli Lilly, KYORIN, Ono, Pfizer, and Takeda.

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