Immune Adverse Events From Nivolumab Predict Better Survival With NSCLC

When immune-related adverse events arise from nivolumab, it may indicate that the therapy is having greater efficacy against non—small-cell lung cancer (NSCLC), as a new study demonstrates a link between these events and improved survival outcomes.

Prior studies have found that the development of immune-related adverse events during a course of immunotherapy is associated with survival benefits for patients with melanoma. A group of oncology researchers from Japan hypothesized that these adverse events may be related to the efficacy of nivolumab in NSCLC, as well. Their findings were published in JAMA Oncology.

In the retrospective study, the records of 134 patients with NSCLC treated with nivolumab were reviewed for any instances of immune-related adverse events, as well as progression-free survival (PFS) and overall survival (OS) to measure efficacy. The comparison between those experiencing adverse events and those who had not was conducted after adjusting for age, sex, prior treatment lines, smoking status, mutational status, and brain metastases.

Some of the most common immune-related adverse events included skin complaints, like rashes, gastrointestinal symptoms, like diarrhea, and general symptoms, like fatigue. Of the 69 total patients who experienced an immune-related adverse event, the majority (57) had less severe symptoms (grade 1 or 2). Just 12 patients experienced grade 3 or 4 adverse events.

A 6-week landmark analysis demonstrated that patients with immune-related adverse events were more likely to have an overall response to treatment than those without (52.3% vs 27.9%; P = .02). They also had significantly higher PFS (median, 9.2 vs 4.8 months; P = .04) and OS (median, not reached vs 11.1 months; P = .01) than the patients who had not experienced adverse events.

These findings are “suggestive of a robust association between such events and survival,” the study authors wrote. Furthermore, because their analyses were conducted in the early stages of treatment, earlier onset of adverse events “might be predictive of response or durable clinical benefit in patients with NSCLC treated with PD-1 inhibitors” like nivolumab.

Although they could not draw conclusions regarding the underlying drivers of the relationship between immune-related adverse events and treatment outcomes, the findings may have important implications for clinical practice, particularly if they are corroborated in larger studies with longer follow-up duration. Clinicians and patients could make more informed treatment decisions, for instance, if they are aware that their side effects are predictive of better survival.

“Early recognition and proper management of immune-related adverse events are important to maximize the therapeutic benefit of immune-checkpoint inhibitors in patients with NSCLC,” the researchers concluded.