Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer

Abstract

PURPOSE Immunotherapy has revolutionized the treatment of advanced non–small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3–5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.

Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

“…This result is consistent with previously published studies [10][11][12][13]. Worse performance status was associated with decreased efficacy of ICIs considering PFS and OS; this result is similar to previous observations [5,7] and consistent with clinical trials [22][23][24].…”

Five-year follow-up of nivolumab treatment in Japanese patients with esophageal squamous-cell carcinoma (ATTRACTION-1/ONO-4538-07)

“…The overall incidence of AEs is similar to that in the primary analysis of ATT RAC TION-1 with a median follow-up of 10.8 months [14]; hence, most AEs tended to appear within a year of nivolumab treatment. The relatively early onset of AEs related to nivolumab treatment has also been observed in other cancers, including malignant melanoma, non-small cell lung cancer, and gastric cancer [12,17,18]. The current study observed that 5 and 2 patients manifested pneumonia as an AE of grade 3-4 and a treatment-related AE of grade 3-4, respectively, after the primary analysis.…”

“…The waterfall plot highlights maximum percent change in the sum of target lesion size from baseline that were assessed by each investigator. Each color represents patients surviving for < 1 (navy blue), 1 (blue), 2 (cyan), 3 (pink), 4 (orange), and 5 (green) years survivors without disease progression were also observed in other tumors treated with nivolumab [10,12].…”

“…In particular, long-term survival with durable responses is a remarkable feature of treatment with immune checkpoint inhibitors [6][7][8][9][10][11][12]. Nivolumab, which is an anti-PD-1 antibody, inhibits interaction between PD-1 and its ligands, such as PD-L1, thereby facilitating the antitumor activity of T lymphocyte [13].…”

The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis

“…Nevertheless, given the limitation of the high heterogeneity of studies included, the findings need to be confirmed by future RCTs focusing on this subject. Because one studies [10] provided pooled OS data of CheckMate-017 [9], and -057 [11], the pooled data were used instead of data from the individual trials in this meta-analysis. The main characteristics of included studies are presented in Table 1.…”