First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Treatment Characteristics and Real-World Progression-Free Survival in Patients with Unresectable Stage III NSCLC who Received Durvalumab After Chemoradiotherapy: Findings from the PACIFIC-R Study.

The Phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC) and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program (EAP). Here, we report treatment characteristics and a pre-planned analysis of real-world progression-free survival (rwPFS). PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every-2-weeks) within an EAP between September-2017 and December-2018. The primary endpoints are investigator-assessed rwPFS and overall survival (analyzed by Kaplan-Meier method). As of November 30, 2020, the full analysis set comprised 1,399 patients from 11 countries (median follow-up duration, 23.5 months). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% CI: 19.1-24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 vs. 19.3 months) and among patients with programmed cell death-ligand 1 (PD-L1) expression ≥1% versus <1% (22.4 vs. 15.6 months). Overall, 16.5% of patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis/interstitial lung disease. Consolidation durvalumab following definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was higher among patients who received concurrent versus sequential CRT and patients with higher PD-L1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors