Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape over the last decade for patients with non–small cell lung cancer (NSCLC), the agents can also stimulate uncontrolled immunity against normal tissues and organs, leading to a cascade of immune-related adverse events (irAEs). These side effects can sometimes lead patients to discontinue these treatments.
However, findings from a large retrospective multicenter study show that a subset of patients with advanced NSCLC who discontinued ICIs due to irAEs continued to experience long-term disease control, including 12.7-month progression-free survival and 43.7-month overall survival. These results may help guide disease management strategies and prognostication among patients who experience severe irAEs, according to the study authors. Findings were published by Pecci et al in Clinical Cancer Research.
Study Methodology
Researchers retrospectively collected and analyzed data from 2,794 patients with advanced NSCLC from two academic centers: Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Clinicopathologic data were abstracted from medical records and reviewed to determine which patients were treated with at least one dose of a PD-L1 inhibitor alone or in combination with a CTLA-4 inhibitor or another immunomodulatory agent from 2011 to 2022. Patients who received a combination of an ICI with chemotherapy or targeted therapy were excluded from the study.
Results
The researchers found that of the 2,794 patients treated with an ICI alone or in combination with other therapies, 10% (n = 271) discontinued the immunotherapy because of an irAE. The median duration of ICI treatment before discontinuation for an irAE was 5.9 months (range = 0.03–73.5 months).
A longer treatment duration before discontinuation for irAEs was associated with improved postdiscontinuation outcomes: for patients on an ICI for < 3 months (n = 89), 3 to 6 months (n = 49), and > 6 months (n =133) before discontinuing for irAE, the median postdiscontinuation progression-free survival was 6.2, 13.9, and 25.8 months (P < .001), respectively, and the median postdiscontinuation overall survival was 21.7, 42.7, and 86.9 months (P < .001), respectively.
At multivariable analyses, predictors of longer postdiscontinuation progression-free survival were a PD-L1 level of ≥ 50%, complete or partial response to treatment, and a treatment duration before discontinuation of between 3 to 6 months and > 6 months. Predictors of longer postdiscontinuation overall response were nonsquamous histology, complete or partial response, and a treatment duration before discontinuation of > 6 months. The use of immunosuppressive agents for toxicity management did not affect postdiscontinuation outcomes.
“A longer treatment duration before discontinuation, a best objective response of [complete or partial response], PD-L1 ≥ 50%, and nonsquamous histology may help clinicians identify patients who may experience long-term disease control after discontinuation of ICI for irAE,” concluded the study authors.
Clinical Significance
“We identified clinical and pathological features that can help physicians to better understand which patients can benefit longer without any additional treatment after discontinuing for toxicity,” said first study author Federica Pecci, MD, a research fellow at Dana-Farber Cancer Institute. “Our study can serve as a valuable resource to support clinicians in the complex considerations of treatment discontinuation for irAEs.”
Mark M. Awad, MD, PhD, of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, is the corresponding author for the Clinical Cancer Research study.
Disclosure: Funding for this study was provided by the National Institutes of Health. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
