SAN FRANCISCO — A stronger, less frequent nivolumab (Opdivo) dosing schedule appeared just as effective to the original dosing of the PD-1 inhibitor for patients with advanced non-small cell lung cancer (NSCLC), a researcher reported here.
The 6-month progression-free survival (PFS) rate was 75% among those assigned to 480-mg nivolumab every 4 weeks compared with 80% for patients assigned to 240-mg nivolumab every 2 weeks, according to Edward B. Garon, MD, of University of California, Los Angeles.
And median PFS was 12.1 months versus 12.2 months, respectively, as presented here at the ASCO-SITC Clinical Immuno-Oncology Symposium.
The trial, originally designed to be a non-inferiority study comparing the two dosing regimens, experienced slow enrollment due to changes in the treatment landscape of advanced NSCLC, not least of which was the FDA approval of the higher-dose nivolumab regimen.
Garon explained that as such, the results presented here were descriptive only and not powered to draw a conclusion, but said there was nothing in the results that would make him concerned that the 480 mg every-4-week dosing schedule would be inferior.
“In many respects extending the dosing frequency of nivolumab fulfills some of the promise of immunotherapy … the idea that we would be able to decrease the medicalization of the lives of our patients,” he said. “For some people, it would lead to them being able to resume a normal work schedule and for others to have fun, to travel on trips that would take longer than a couple weeks.”
Study discussant Siwen Hu-Lieskovan, MD, PhD, of the Huntsman Cancer Institute in Salt Lake City, agreed that the nivolumab 480 every 4 weeks regimen demonstrated convincing short-term safety data and was suggestive of non-inferiority. But she noted that the enrolled patients had established benefit to the lower-dose, more-frequent schedule, so the trial was really looking at the less-frequent regimen in a maintenance setting.
The long-term impact on efficacy, durability, and overall survival “still remain to be determined,” Hu-Lieskovan said.
Moving beyond this trial, Hu-Lieskovan said that administration could possibly be made even more convenient by researching the use of subcutaneous injections, and, eventually, making nivolumab a small molecule to allow oral administration.
CheckMate-384 enrolled patients with advanced NSCLC who had been exposed to nivolumab for 12 months or less. Patients were randomly assigned to 240 mg every 2 weeks or 480 mg every 4 weeks, and treated for up to 2 years. Data presented were from 329 of 363 enrolled patients.
Overall, PFS was similar between the two study arms. Subgroup analyses suggested that the 480-mg regimen may have greater PFS benefit in patients with two or more prior lines of therapy (76% for 480 mg vs 61% for 240 mg), and those who had from 9 to 12 months prior exposure to the study drug (92% for 480 mg vs 77% for 240 mg).
Data on the co-primary endpoint of PFS at 1 year (53% in both arms) were included in the abstract but not presented.
There was a numerically higher rate of treatment-related adverse events (TRAEs) with the lower-dose, higher-frequency regimen (61% vs 48%). Garon said the discrepancy might be related to the bias of patients coming into the clinic more frequently, and, therefore, having more opportunity to discuss these events.
Rates of serious TRAEs and events leading to discontinuation were similar between the two arms.
Garon and colleagues, and Hu-Lieskovan have received research funding and/or honoraria from various industry entities.