Patients with advanced melanoma who are treated with nivolumab after their first disease progression may experience tumor response without compromising safety, according to an original investigation published in JAMA Oncology (published online June 29, 2017; doi:10.1001/jamaoncol.2017.1588).
Immune checkpoint inhibitors such as nivolumab have demonstrated atypical response patterns, which are often not fully captured by conventional clinical trial response criteria. There exists a general need to better understand the potential benefits of continued immune checkpoint inhibition beyond progression.
Georgina Long, PhD, melanoma oncology and translational research, Melanoma Institute (Australia), and colleagues evaluated the safety and potential benefit of nivolumab monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression in melanoma. The retrospective analysis consisted of 526 treatment-naïve patients with advanced disease, some of whom (n = 85) continued nivolumab treatment beyond progression in multiple phase III clinical trials from 2015 to 2017.
Patients were categorized as either those who received their last dose of nivolumab more than six weeks after progression (TBP group) or those not treated beyond progression who discontinued therapy before or at progression (non-TBP group). Patients were treated beyond progression if deriving apparent clinical benefit and tolerating treatment, at the investigator’s discretion.
Researchers found that a substantial proportion of patients treated with frontline nivolumab who were clinically stable and eligible for treatment beyond RECIST v1.1-defined progression demonstrated clinical benefit without compromising safety. Twenty-eight percent of patients who continued to receive nivolumab after disease progression achieved a target lesion reduction of at least 30% compared to baseline. Treatment-related adverse events were similar in both groups, even in most grade 3-4 adverse events.
Limitations of the study include its retrospective nature and the relatively small sample size of patients treated beyond disease progression. Nonetheless, further analysis is warranted to validate the study’s findings.
“The possibility of delayed immune-related responses suggests that patients with disease progression could benefit from continued treatment with immune checkpoint inhibitors," authors wrote.—Zachary Bessette