Nivolumab (nivo), a fully human immunoglobulin (Ig) G4 PD-1 immune checkpoint inhibitor, is approved in the United States for patients with previously treated metastatic non–small-cell lung cancer (NSCLC) and in the European Union for pretreated locally advanced or metastatic squamous (SQ) NSCLC, based on results of 2 phase 3 trials.1-4 In the current analysis by Borghaei and colleagues,5 patients with SQ (CheckMate-017) or nonsquamous (NSQ; CheckMate-057) NSCLC received nivo 3 mg/kg every 2 weeks or docetaxel (doc) 75 mg/m2 every 3 weeks (1:1 randomization) until progression or discontinuation due to toxicity/other reasons. The primary clinical end point in each study was overall survival (OS). Multivariate exploratory analyses of baseline serum cytokines were performed separately in patients with SQ and NSQ NSCLC. An SQ-cytoscore derived from evaluable patients in CheckMate-017 and CheckMate-063 (single-arm phase 2 study of nivo in SQ NSCLC) and a NSQ-cytoscore derived from evaluable patients in CheckMate-057 were generated to quantify the effect of each identified cytokine set on OS (using 18-month data cutoffs). Cytoscores were defined as high or low based on the median cutoffs. In CheckMate-017, median OS (mOS) was 9.2 months versus 6.0 months with nivo versus doc (18-month OS, 28% vs 13%; hazard ratio [HR], 0.62 [0.48-0.81]; P = 0.0004). In CheckMate-057, mOS was 12.2 months versus 9.4 months with nivo versus doc (18-month OS, 39% vs 23%; HR, 0.72 [0.60-0.88]; P = 0.0009). A greater magnitude of benefit was noted for patients with PD-L1–expressing NSQ NSCLC; PD-L1 expression was neither prognostic nor predictive of benefit in patients with SQ NSCLC. Treatment-related adverse events were less frequent with nivo versus doc in both trials. Preliminary results show an association of SQ- and NSQ-cytoscores with OS (Table). The authors concluded that nivo results in improved OS and a favorable safety profile versus doc across NSCLC histologies. Select sets of baseline serum cytokines were found to be associated with OS benefit in patients with advanced SQ and NSQ NSCLC.
The 2-year update of these data demonstrated durable, long-term improved OS and PFS with nivo compared with doc. Two-year OS rates were 29% with nivo compared with 16% with doc in NSQ patients and 23% versus 15% in patients with SQ disease; this difference was most pronounced (45% vs 13%) in patients with PD-L1 expression ≥10%. Similarly, 2-year PFS was 16% with nivo compared with 7% with doc (NSQ) and 12% versus 1% (SQ). The occurrence of treatment-related adverse events was not significantly different at 2 years compared with 1 year of therapy.
The authors conclude that at 2 years of follow-up, nivo demonstrated durable, long-term OS and PFS advantages versus doc in previously treated patients with advanced SQ or NSQ NSCLC, with no change in safety profile. In general, cytoscores were not associated with treatment effect, and, therefore, were not predictive of benefit from nivo.
