Study Title: Factors associated with disease progression after discontinuation of immune checkpoint inhibitors for immune-related toxicity in patients with advanced non-small cell lung cancer
Publication: Clinical Cancer Research
Corresponding Dana-Farber Cancer Institute authors: Federica Pecci, MD, Mark Awad, MD, PhD, Memorial Sloan Kettering
Summary: Dana-Farber Cancer Institute investigators, in collaboration with Memorial Sloan Kettering, found that the cancer-controlling effects of immune checkpoint inhibitors continues even after treatment is stopped due to immune-related adverse events (irAEs) for patients with advanced non-small cell lung cancer (NSCLC). The team accessed medical records at both locations to identify patients with advanced NSCLC who had been treated with one or more immune checkpoint inhibitors (ICIs) but not with chemotherapy or a targeted therapy. Of those patients, 10% discontinued ICIs due to irAEs. Disease control however, continued even after treatment stopped, with increased post-discontinuation clinical outcomes observed in patients who received ICI before discontinuation for at least 6 months, and who had high levels of PD-L1 expression in their tumors (≥50%), non-squamous histology, and for those whose tumors shrank while taking the ICI. Use of immunosuppressive agents for immune-related toxicity management did not impact post-discontinuation outcomes.
Significance: Between 3 and 25% of patients with advanced non-small cell lung cancer who receive immune checkpoint inhibitors alone or in combination as treatment discontinue treatment due to intolerable side effects. Deciding to discontinue treatment can be stressful because consequences of doing so are not clear. This study provides information to physicians to help them work with patients in weighing benefits and risks of discontinuing ICI therapy.
While discontinuation is necessary for severe adverse events, managing grade 2 irAEs poses a more intricate challenge for clinicians. These cases require carefully weighing the patient's reported discomfort against the potential risks and benefits of continuing or interrupting ICIs therapy. In this context, clinicopathologic features such as PD-L1 expression, TMB, histology, and treatment best response, as demonstrated in our study, can serve as valuable tools to guide clinical decision-making and facilitate informed discussions with patients.
Funding: The National Institutes of Health
