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.

• Authors: S Sugawara, J-S Lee, J-H Kang, H R Kim, N Inui, T Hida, K H Lee, T Yoshida, H Tanaka, C-T Yang, M Nishio, Y Ohe, T Tamura, N Yamamoto, C-J Yu, H Akamatsu, Y Namba, N Sumiyoshi, K Nakagawa
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 32 Issue 9 Pg. 1137-1147 (09 2021) ISSN: 1569-8041 [Electronic] England
• PMID: 34139272 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Proto-Oncogene Proteins
• Bevacizumab
• Nivolumab
• Carboplatin
• Protein-Tyrosine Kinases
• Paclitaxel

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Bevacizumab (adverse effects)
• Carboplatin (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Double-Blind Method
• Humans
• Lung Neoplasms (drug therapy)
• Neoplasm Recurrence, Local (drug therapy)
• Nivolumab (adverse effects)
• Paclitaxel (adverse effects)
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins