Nivolumab versus docetaxel in previously treated advanced non-small cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases
Menés sur 854 patients atteints d'un cancer du poumon non à petites cellules de stade avancé et de métastases hépatiques, ces deux essais de phase III comparent l'efficacité, du point de vue de la survie globale, et la toxicité du nivolumab et du docétaxel (durée minimale de suivi : 3 ans)
Background : Long-term data with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti–programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and non-squamous (CheckMate 057) NSCLC. We report results from ≥3 years’ follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods : Patients were randomized 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary endpoint of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results : After 40.3 months’ minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% (95% confidence interval [CI], 14–21%) versus 8% (95% CI, 6–11%) in the pooled population with squamous or non-squamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions : After 3 years’ minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.Clinical trial registrationCheckMate 017: NCT01642004; CheckMate 057: NCT01673867
Annals of Oncology 2018