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Background: 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.Methods: 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.Results: 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.Conclusions: 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 .). [ABSTRACT FROM AUTHOR]

Purpose/objective(s): We hypothesized that the addition of concurrent ipilimumab (IPI) with chemoradiotherapy followed by consolidative nivolumab (NIVO) would be safe and tolerable for patients with unresectable stage III non-small cell lung cancer (NSCLC). We report early outcomes and toxicity associated with this regimen in a phase I/II clinical trial.Materials/methods: The study was designed as a prospective, multicenter phase I/II trial. Eligible patients had ECOG 0-1 and unresectable stage III NSCLC. Therapy included a platinum-based chemotherapy doublet with concurrent radiotherapy to 60 Gy in 30 fractions over six weeks and two doses of concurrent IPI (1 mg/kg) given weeks 1 and 4. Maintenance NIVO was initiated 1-3 weeks after completion of chemoradiotherapy/IPI and given every 4 weeks (480 mg) for up to 12 cycles. The primary endpoints were to evaluate the safety and tolerability of the regimen (Phase I) and the 12-month PFS (Phase II). Treatment-related toxicity was assessed according to CTCAE v5.0. Time to event analysis was performed with Kaplan Meier (KM) and Cox proportional hazard (CPH) models. Results are reported with 95% confidence intervals (CI).Results: Nineteen of a planned 55 patients were enrolled in the trial which was discontinued without proceeding to the Phase II component due to exceeding the futility boundary for toxicity. The median follow-up was 21 months by the reverse KM method. The 12-month PFS estimate was 54% (CI 29-78) and the median PFS was 19 months (CI 6-not reached). The 12-month OS estimate was 60% (CI 36-84) while the median OS was not reached. Ten patients (53%, CI 29-76) experienced grade 2 or higher (G2+) pneumonitis. The median time to development of G2+ pneumonitis was 5.5 months and the risk of G2+ pneumonitis at 6- and 12-months was 57% (CI 30-84) and 74% (CI 49-99), respectively. Sixteen patients (84%, CI 68-100) had any G3+ treatment related toxicity. The most common G3+ toxicities were pulmonary (8 patients, 42%, CI 20-67) and cytopenias (7 patients, 37%, CI 16-62). Five patients (26%, CI 6-46) had possible treatment related G5 toxicity, including three patients with possible treatment related G5 pulmonary toxicity (16%, CI 0-32). There was no difference in the mean percent of lung volume receiving 20 Gy (V20) between those with and without G2+ pneumonitis (26%, CI 20-32 vs 21%, CI 16-27, P = 0.18), nor in the mean lung dose (14 Gy, CI 10-17 vs 15 Gy, CI 12-18, P = 0.35). Neither mean lung dose nor lung V20 were associated with time to G2+ pneumonitis on univariable CPH.Conclusion: The combination of concurrent IPI with standard chemoradiation followed by maintenance NIVO for unresectable stage III NSCLC is associated with significant toxicity which may limit opportunities for improved outcomes, although the sample size in this trial is small. Alternative strategies or sequencing should be explored to integrate immunotherapy with cytotoxic chemotherapy and radiation for patients with unresectable stage III NSCLC. [ABSTRACT FROM AUTHOR]