2019 ASCO-SITC: Efficacy and Safety of Less Frequent Dosing of Second-Line Nivolumab for Non–Small Cell Lung Cancer


Key Points

  • A total of 329 previously treated patients with advanced NSCLC were randomly assigned to receive nivolumab 480 mg every 4 weeks or 240 mg every 2 weeks.
  • Investigators evaluated the safety and efficacy of the every-4-week regimen of nivolumab vs the every-2-week schedule.
  • An every-4-week regimen of nivolumab at 480 mg is comparable to an every-2-week regimen at 240 mg, and may offer a more convenient treatment option.

Researchers reported similar efficacy and safety with an every-4-week regimen of nivolumab in the second-line setting compared to an every-2-week schedule in patients with non–small cell lung cancer (NSCLC). Edward B. Garon, MD, and colleagues presented the results of an interim analysis of the phase IIIb/IV CheckMate 384 trial at then 2019 ASCO-SITC Clinical Immuno-Oncology Symposium (Abstract 100). Dr. Garon is Associate Clinical Professor of Hematology/Oncology and Medicine at the David Geffen School of Medicine at the University of California, Los Angeles.

CheckMate 384

CheckMate 384 was designed as a noninferiority study with a planned enrollment of 600 patients. Changes in the treatment armamentarium for NSCLC made it difficult to enroll patients in the second-line setting, because most patients in the study population are receiving an immune checkpoint inhibitor in the front-line setting.  The sample size of the study was reduced as a result, and the enrollment was stopped early. The study was changed from a noninferiority study to include a descriptive analysis only.

A total of 329 patients were randomly assigned to receive a 30-minute infusion of nivolumab at a dose and schedule of either 480 mg every 4 weeks (n = 166) or 240 mg every 2 weeks (n = 163). All patients were previously treated with nivolumab at 3 mg/kg, or 240 mg, every 2 weeks for up to 12 months, and all patients responded to previous treatment (complete response, partial response, or stable disease). Randomization was stratified by prior response to nivolumab (ie, complete or partial response or stable disease, and squamous or nonsquamous tumor histology). The primary endpoints of CheckMate 384 were progression-free survival at 6 months and 1 year. Safety was a secondary endpoint.

Interim Analysis of Safety and Efficacy

At a median follow-up of 9.5 and 10.2 months, respectively, patients treated with 480 mg every 4 weeks (n = 164) showed similar rates of progression-free survival compared to patients who received 240 mg of nivolumab every 2 weeks (n = 161). Investigators reported that safety was also similar between the two groups. Treatment-related adverse events of any grade were reported in 48% of patients receiving nivolumab every 4 weeks and 61% of patients receiving nivolumab every 2 weeks. The most common adverse events were diarrhea, hypothyroidism, and fatigue. Adverse events leading to drug discontinuation were reported in 6% of patients receiving treatment every 4 weeks vs 9% of those receiving treatment every 2 weeks. There were no reports of treatment-related death.


Nivolumab is approved at 240 mg every 2 weeks in the European Union and Japan; in the United States and Canada, nivolumab is approved at 240 mg every 2 weeks, or 480 mg every 4 weeks, in the second-line treatment of patients with advanced NSCLC. The investigators concluded that nivolumab administered every 4 weeks at a dose of 480 mg showed similar efficacy and safety as the every-2-week schedule. They added that administering nivolumab every 4 weeks at a dosage of 480 mg could offer a more convenient option in the second-line treatment of patients with advanced NSCLC. A final analysis is planned once all study participants have at least 12 months of follow-up.

Disclosure: The study authors' full disclosures can be found at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.