Immune checkpoint inhibitors (ICIs) are largely considered a game-changer for patients with non-small cell lung cancer (NSCLC), delivering survival benefits in both early and advanced stages of the disease. However, between 3% and 12% of patients treated with a single ICI, and up to 25% of patients treated with immunotherapy combinations, must discontinue treatment due to immune-related adverse events (irAEs).
“When immunotherapy activates the immune system, the goal is to selectively target cancer cells. But this activation can also cause inflammation in other organs,” said Mark Awad, MD, PhD, in a recent press release from the American Association for Cancer Research (AACR). “Whenever we see these side effects, we question whether we should keep giving immunotherapy or if we need to stop treatment temporarily or permanently.”
Until recently, clinical outcomes following ICI treatment discontinuation were largely unknown, leaving many patients to face uncertainty about the return or worsening of their cancer.
Now, findings from a study published in the AACR journal Clinical Cancer Research suggest that some patients may continue to experience disease control after stopping ICI treatment.
Patient Outcomes After Immunotherapy Discontinuation
In the study, Dr. Awad, Chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, and colleagues aimed to characterize post-discontinuation outcomes among patients with advanced NSCLC who stopped ICI therapy due to side effects.
Of the 2,794 enrolled participants, approximately 10% stopped treatment due to irAEs.1 The median duration of ICI treatment before discontinuation was nearly 6 months.1 Yet, many continued to experience disease control after stopping treatment.
Longer treatment duration before ICI discontinuation was associated with improved post-discontinuation progression-free survival (PFS):1
- 6.2 months for patients treated for less than 3 months
- 13.9 months for those treated for 3 to 6 months
- 25.8 months for patients for more than 6 months1
The study also demonstrated a similar trend for overall survival (OS) following treatment discontinuation:1
- 21.7 months for those who discontinued within 3 months
- 42.7 months among patients who received treatment for 3 to 6 months
- 86.9 months for those who received treatment for more than 6 months1
Predicting Long-Term Outcomes in Patients with NSCLC
In a multivariable analysis, predictors of longer post-discontinuation PFS included PD-L1 expression of 50% or higher, a complete response or partial response (CR/PR) to treatment, and treatment duration before discontinuation of 3 to 6 months or more than 6 months.1
Similarly, predictors of longer post-discontinuation OS were non-squamous histology, CR/PR to therapy, and treatment duration of more than 6 months before discontinuation.1
Additionally, the use of immunosuppressive agents for toxicity management did not negatively affect outcomes after treatment discontinuation.1
“We identified clinical and pathological features that can help physicians better understand which patients can benefit longer without any additional treatment after discontinuing for toxicity,” said Federica Pecci, MD, a research fellow at Dana-Farber Cancer Center.
Although treatment discontinuation is sometimes necessary to manage severe irAEs, the study suggests that the discontinuation of ICI doesn’t necessarily mean the end of its benefits. Furthermore, the findings may help physicians better predict individual patient outcomes and assess the risk of disease progression following immunotherapy discontinuation.
“Our study can serve as a valuable resource to support clinicians in the complex considerations of treatment discontinuation for irAEs,” Dr Pecci said.
References
- 1. Federica Pecci, Rohit Thummalapalli, Stephanie L. Alden, Biagio Ricciuti, Joao V. Alessi, Arielle Elkrief, Hira Rizvi, Xinan Wang, Mark Jeng, Jacklynn V. Egger, Victor R. Vaz, Adriana Barrichello, Giuseppe Lamberti, Alessandro Di Federico, Valentina Santo, Guilherme Rossato de Almeida, Malini Gandhi, Phoebe Clark, Mizuki Nishino, Bruce E. Johnson, Matthew Hellmann, Adam J. Schoenfeld, Mark M. Awad; Factors Associated with Disease Progression after Discontinuation of Immune Checkpoint Inhibitors for Immune-Related Toxicity in Patients with Advanced Non–Small Cell Lung Cancer. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-2990
