Cancer Treatment

Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: Checkmate 451

In the April 20, 2021 edition of JCO, investigators report on the results of the CheckMate 451 trial.


Patients with extensive stage small cell lung cancer, unfortunately do not obtain durable responses to platinum based chemotherapy. Investigators from the CheckMate 451 trial assessed the utility of maintenance immunotherapy after induction therapy with platinum based chemotherapy for extended stage small cell lung cancer.


Patients were randomized in a one-to-one -one fashion to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg every 2 weeks, or nivolumab 240 mg once every 2 weeks, or placebo for up to 2 years, in patients who had shown no progression after </= 4 cycles of first-line chemotherapy.  The primary endpoint was overall survival with nivolumab plus ipilimumab versus placebo.  Secondary endpoints were hierarchically tested.


834 patients were randomly assigned.  The minimum follow-up was 8.9 months.  The median overall survival, 9.2 versus 9.6 months, was not significantly prolonged with nivolumab plus ipilimumab versus placebo, hazard ratio 0.92, 95% confidence interval 0.75–1.12, P = 0.37.  In the nivolumab versus placebo analysis, the hazard ratio for overall survival was 0.84, 95% confidence interval 0.69–1.02, with a median overall survival for nivolumab of 10.4 months.  The hazard ratio associated with progression free survival versus placebo was 0.72 for nivolumab plus ipilimumab, 95% confidence interval, 0.60–0.87 and 0.67 for nivolumab, 95% confidence interval, 0.56–0.81.  The authors noted a trend towards overall survival benefit, with nivolumab plus ipilimumab in patients with tumor mutational burden of at least 13 mutations/Megabase.  With regards to grade 3 and 4 treatment-related adverse events, 52.5% were seen in patients with the combination of nivolumab and ipilimumab versus 11.5% from nivolumab monotherapy and 8.4% for placebo.


The authors concluded “Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.”


Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Stage Small-Cell Lung Cancer: Checkmate 451

In the April 20, 2021 edition of Journal of Clinical Oncology, Taofeek K. Owonikoko and colleagues report on the results of the Checkmate 451 trial.