Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced non-squamous non-small cell lung cancer
Mené sur 550 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde de stade avancé, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du nivolumab à un traitement de première ligne combinant carboplatine, paclitaxel et bévacizumab
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 non-squamous 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 non-squamous 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 6 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 vs. 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 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 non-squamous NSCLC.