Encouraging Results After Discontinuation of Cancer Immunotherapy Due to Immune AEs

Oncology/Hematology
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Lung Cancer

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Durable benefits in advanced non-small cell lung cancer, depending on treatment duration

by
Charles Bankhead, Senior Editor, MedPage Today
April 18, 2025 • 4 min read

Patients stopping immunotherapy due to side effects still experienced long-term benefits, with survival extending beyond 7 years.Factors predicting longer survival after treatment discontinuation included high PD-L1 expression, positive treatment response, and longer treatment duration.The results provided some reassurance in an area of uncertainty regarding outcomes after discontinuing immunotherapy because of immune-related adverse events.

Patients who discontinued cancer immunotherapy because of immune-related adverse events (irAEs) often had durable benefits despite not receiving the planned course of treatment, a retrospective study of patients with lung cancer showed.

Patients who stopped treatment early had a median post-discontinuation survival ranging as high as 7-plus years, depending on the duration of treatment before stopping therapy. In a multivariable analysis, predictors of longer post-discontinuation progression-free survival (PFS) were PD-L1 expression ≥50, complete or partial response to treatment, and treatment duration of 3-6 months or >6 months. Treatment duration, objective response, and non-squamous histology were significant predictors of post-discontinuation overall survival (OS).

Among patients who stopped treatment within 3 months because of irAEs, 42% did so because of grade 2 irAEs, suggesting opportunities to help patients stay on therapy longer, reported Mark Awad, MD, of Dana-Farber Cancer Institute in Boston, and coauthors in Clinical Cancer Research.

“Although discontinuation is necessary for severe adverse events, managing [a grade 2] irAE poses a more intricate challenge to clinicians,” the authors stated. “These cases require carefully weighing the patient’s reported discomfort against the potential risks and benefits of continuing or interrupting ICI [immune checkpoint inhibitor] therapy. In this context, clinicopathologic features … 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.”

The study is important because it provides reassurance to oncologists and patients that durable benefits are possible in many cases after discontinuing treatment because of irAEs, said Michael Wong, MD, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York.

“Patients are concerned about stopping treatment because of toxicity,” Wong told MedPage Today. “Is this going to impair my chance of survival? Is this considered treatment failure? Will I have an earlier death? The answer from this study is ‘no.’ This is not considered treatment failure. This paper shows that individuals who exhibit immunotoxicity can have very long and good outcomes.”

“Immunotoxicity tells you that your immune system is triggered,” he continued. “When I give immunotherapy to a patient, I worry about whether it is working. With chemotherapy your hair falls out, your blood counts go down, so we know we’re having a positive impact on the biology. With immunotherapy, you don’t have that kind of signal. Immunotoxicity is a signal that you have activated your immune system. You get colitis, you get continuous toxicity. If you look at the side effects listed in the paper, there is nothing extraordinary, just the standard side effects you get with immunotherapy.”

Patients also want to know whether they should resume therapy at some point, said Wong. The findings from the study suggest that is not necessary, particularly when patients have received 3 to 6 months of treatment or more.

Despite showing an association between treatment duration and outcomes, the study did not address the larger question of how much treatment is enough.

“I sit on sort of a guideline panel, and the question that always comes up is ‘how much is enough?’ — and we don’t have the answer,” said Wong. “I always remind students that [immunotherapy] is not about response rates, in terms of how much tumor shrinkage we get. We’re in the business of helping people live longer. This study gives us some confidence that we don’t have to keep going [with treatment].”

Despite transforming treatment for many types of cancer, immunotherapy with ICIs can stimulate uncontrolled immune reactions against normal tissues, leading to irAEs, Awad and coauthors noted. The types and frequencies of irAEs differ by tumor type and ICI regimen, but most often involve the gastrointestinal tract, endocrine glands, and skin. Current guidelines suggest discontinuation of treatment when severe irAEs occur.

The clinical course for patients with non-small cell lung cancer (NSCLC) after discontinuing ICIs because of irAEs is heterogeneous, the authors continued. Predictive factors have remained largely unknown. To contribute to the knowledge base, Awad and colleagues retrospectively evaluated outcomes in patients who discontinued ICI treatment for NSCLC because of irAEs.

The analysis included 2,794 patients treated at two centers from 2011 to 2022. Patients who received combination immunotherapy or an ICI combined with chemotherapy or a targeted agent were excluded.

Records showed that 271 patients (10%) discontinued treatment because of irAEs after a median treatment duration of 5.9 months. Discontinuation occurred within 3 months in 89 cases, 3-6 months in 49, and >6 months in 133 cases. The results showed that longer treatment duration before discontinuation was significantly (P