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Randomized Controlled Trial
. 2023 Aug;12(16):17061-17067.
doi: 10.1002/cam4.6348. Epub 2023 Aug 28.

First-line nivolumab, paclitaxel, carboplatin, and bevacizumab for advanced non-squamous non-small cell lung cancer: Updated survival analysis of the ONO-4538-52/TASUKI-52 randomized controlled trial

Hye Ryun Kim  1 , Shunichi Sugawara  2 , Jong-Seok Lee  3 , Jin-Hyoung Kang  4 , Naoki Inui  5 , Toyoaki Hida  6 , Ki Hyeong Lee  7 , Tatsuya Yoshida  8 , Hiroshi Tanaka  9 , Cheng-Ta Yang  10 , Makoto Nishio  11 , Yuichiro Ohe  8 , Tomohide Tamura  12 , Nobuyuki Yamamoto  13 , Chong-Jen Yu  14 , Hiroaki Akamatsu  13 , Shigeru Takahashi  15 , Kazuhiko Nakagawa  16
Affiliations
Randomized Controlled Trial

First-line nivolumab, paclitaxel, carboplatin, and bevacizumab for advanced non-squamous non-small cell lung cancer: Updated survival analysis of the ONO-4538-52/TASUKI-52 randomized controlled trial

Hye Ryun Kim et al. Cancer Med. 2023 Aug.

Abstract

Background: ONO-4538-52/TASUKI-52 was performed in Japan, Korea, and Taiwan to determine the oncological effectiveness and safety of combining nivolumab or placebo with bevacizumab plus platinum chemotherapy for the initial (first-line) treatment of patients with advanced non-squamous non-small cell lung cancer (nsNSCLC). At the interim analysis (minimum follow-up, 7.4 months), the independent radiology review committee-assessed progression-free survival was significantly longer in the nivolumab arm, but overall survival (OS) data were immature.

Methods: Here, we present the updated OS data. Patients with treatment-naïve stage IIIB/IV or recurrent nsNSCLC without driver mutations in ALK, EGFR, or ROS1, were randomized 1:1 to receive either nivolumab or placebo. Patients in both arms received paclitaxel, carboplatin, and bevacizumab, administered 3-weekly for a maximum of 6 cycles. Nivolumab/placebo and bevacizumab were subsequently continued until disease progression or unacceptable toxicity.

Results: Overall, 550 patients were randomized. At the time of the analysis (minimum follow-up: 19.4 months), the median OS was longer in the nivolumab arm than in the placebo arm (30.8 vs. 24.7 months; hazard ratio 0.74, 95% confidence interval 0.58-0.94). The 12-month OS rates were 81.3% vs. 76.3% in the nivolumab vs. placebo arms, respectively. The respective 18-month OS rates were 69.0% vs. 61.9%.

Conclusion: Nivolumab plus platinum chemotherapy and bevacizumab demonstrated longer OS vs. the placebo combination. We believe this regimen is viable as a standard, first-line treatment for patients with advanced nsNSCLC without driver mutations in ALK, EGFR, or ROS1.

Trial registration: ClinicalTrials.gov NCT03117049.

Keywords: bevacizumab; chemotherapy; nivolumab; non-squamous non-small cell lung cancer; survival.

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Conflict of interest statement

Ono Pharmaceutical Co., Ltd. and Bristol‐Myers Squibb funded the study, provided the study drugs, and were involved in the collection, analysis, and interpretation of the data. Employees of the sponsors reviewed and commented on the manuscript. The authors had full access to the data and took final responsibility for the decision to publish the manuscript.

The authors report the following disclosures; remuneration of 1 million yen or more: S.T. (Ono Pharmaceutical); lecture fees/honoraria/other fees of 500,000 yen or more: H.‐R.K. (Ono Pharmaceutical, AstraZeneca, Roche, Boehringer Ingelheim), S.S. (Ono Pharmaceutical, Bristol‐Myers Squibb), T.H. (Ono Pharmaceutical, Bristol‐Myers Squibb), K.‐H.L. (Bristol‐Myers Squibb, MSD, AstraZeneca, Pfizer, and Eli Lilly), T.Y. (Ono Pharmaceutical, Chugai, AstraZeneca), H.T. (AstraZeneca, Chugai), C.‐T.Y. (Ono Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Chugai, Pfizer, Takeda, Novartis, Roche, Eli Lilly, Merck, MSD), M.N. (Ono Pharmaceutical, Bristol‐Myers Squibb), Y.O. (AstraZeneca, Chugai), T.T. (Cmic ShiftZero), H.A. (AstraZeneca), N.Y. (MSD, AstraZeneca, Chugai, Eli Lilly, Boehringer‐Ingelheim, Pfizer, Ono Pharmaceutical, Takeda), K.N. (Eli Lilly, Chugai, Ono Pharmaceutical); annual contract research grants of 1 million yen or more: H.‐R.K (Ono Pharmaceutical), S.S. (Ono Pharmaceutical, Bristol‐Myers Squibb), J.‐S.L. (Ono Pharmaceutical), J.‐H.K. (Ono Pharmaceutical), N.I. (Ono Pharmaceutical), T.H. (Ono Pharmaceutical, Bristol‐Myers Squibb), K.‐H.L. (Ono Pharmaceutical), T.Y. (Ono Pharmaceutical, Chugai, AstraZeneca, Amgen, Novartis, Bristol‐Myers Squibb, Takeda), H.T. (Ono Pharmaceutical), C.‐T.Y. (Ono Pharmaceutical), M.N. (Ono Pharmaceutical, Bristol‐Myers Squibb), Y.O. (AstraZeneca, Chugai, Eli Lilly, Ono Pharmaceutical, Bristol‐Myers Squibb, Kirin, Dainippon‐Sumitomo, Pfizer, Taiho, Novartis, Takeda, Kissei, Daiichi‐Sankyo, Janssen, LOXO), N.Y. (Chugai, Toppan printing, Cmic ShiftZero, MSD, Pfizer, PPD, IQVIA, Eli Lilly, A2 healthcare, Boehringer Ingelheim, Terumo, Takeda, AstraZeneca, Amgen, Jansen, Taiho, Ono Pharmaceutical), C.‐J.Y. (Ono Pharmaceutical), H.A. (Chugai, Amgen), K.N. (Ono Pharmaceutical, MSD, Daiichi Sankyo, Taiho, Chugai, SYNEOS HEALTH CLINICAL, Japan Clinical Research Operations, AstraZeneca, IQVIA Services JAPAN, Covance Japan, Takeda, GlaxoSmithKline, Sanofi, EPS Corporation, Novartis, Medical Research Support); scholarship/endowments of 1 million yen or more: N.Y. (Taiho, Chugai, Daiichi‐Sankyo, Ono Pharmaceutical), K.N. (Takeda, Chugai, Ono Pharmaceutical). Y.O. is a member of the editorial board of Cancer Science.

Figures

FIGURE 1
FIGURE 1
Overall survival with a minimum follow‐up period of 19.4 months (Kaplan–Meier plot). CI, confidence interval; HR, hazard ratio; OS, overall survival; mo, months.
FIGURE 2
FIGURE 2
Subgroup analysis of overall survival. CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; mo, months; NR, not reached; OS, overall survival; PD‐L1, programmed death‐ligand 1.
FIGURE 3
FIGURE 3
Overall survival in patients stratified by programmed death‐ligand 1 expression level (Kaplan–Meier plots). There were five patients with indeterminate PD‐L1 expression levels in both arms. CI, confidence interval; HR, hazard ratio; mo, months; OS, overall survival; PD‐L1, programmed death‐ligand 1; NR, not reached.
See this image and copyright information in PMC

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