Can Patients With NSCLC Experience Durable Disease Control After ICI Discontinuation?

Certain patients with non–small cell lung cancer (NSCLC) who discontinued immune checkpoint inhibitor therapy due to immune-related adverse events (irAEs) “continued to experience long-term disease control,” according to a recent study.

Senior author Mark Awad, MD, PhD, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, and first author Federica Pecci, MD, a research fellow at Dana-Farber Cancer Institute, published findings from the study in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).

It was important to conduct the research because while immune checkpoint inhibitors have “revolutionized the treatment landscape” for NSCLC by “offering significant survival benefits in both early-stage and advanced disease,” irAEs can occur, according to a news release on the study from the AACR. These irAEs include pneumonitis, colitis, and hepatitis, which may lead to permanent treatment discontinuation.

For example, between 3% and 12% of patients who receive treatment with a single immune checkpoint inhibitor may need to discontinue treatment due to irAEs, with that proportion being up to 25% in those who receive dual immune checkpoint inhibitor combination therapy.

“When immunotherapy activates the immune system, the goal is to selectively target cancer cells. But this activation can also cause inflammation in other organs,” Dr. Awad said in a statement provided by 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.”

With many patients having concerns about whether their cancer will progress or recur if they stop treatment with immune checkpoint inhibitors, it was critical for Dr. Awad and colleagues to characterize the outcomes of patients with NSCLC who discontinued treatment with immune checkpoint inhibitors. They also evaluated clinical and pathologic characteristics that were associated with longer progression-free survival (PFS) and overall survival (OS) after treatment discontinuation.

Dr. Awad and colleagues evaluated a multi-institutional cohort that included 2,794 patients who received treatment with immune checkpoint inhibitors alone or in combination with other therapies. They found that around 10% of these patients discontinued treatment because of irAEs.

The study showed that among these patients, the median post-discontinuation PFS was 12.7 months, with a median post-discontinuation OS of 43.7 months.

“These outcomes suggest that patients can experience prolonged disease control and survival after stopping treatment due to toxicity or if side effects are impacting their quality of life,” Dr. Pecci said in a statement provided by the AACR.

The study investigators broke down the data and outcomes by how long patients had received immune checkpoint inhibitor therapy before discontinuing it.

Less than 3 months of therapy: Median PFS after discontinuation, 6.2 months; median OS after discontinuation, 21.7 months

Between 3 and 6 months of therapy: Median PFS after discontinuation, 13.9 months; median OS after discontinuation, 42.7 months

More than 6 months: Median PFS after discontinuation, 25.8 months; median OS after discontinuation, 86.9 months

The researchers also conducted a multivariable analysis, finding that predictors of longer post-discontinuation PFS included:

• High PD-L1 expression
• Complete or partial response to treatment
• Treatment duration of either 3 to 6 months or more than 6 months before discontinuation

The multivariable analysis showed that factors associated with a prolonged post-discontinuation OS were:

• Nonsquamous histology
• Complete or partial response to treatment
• Treatment duration exceeding 6 months

In addition, when it came to managing irAEs, the study showed that the use of steroids or other immunosuppressants was “not associated with a difference in PFS or OS after discontinuation in the study, suggesting that such treatments may not jeopardize the anticancer response.”

Officials explained that it’s important to recognize that limitations of this study include its retrospective design, “which could be hindered by missing or inaccurate data annotations.” It’s also critical to note that “comparisons based on treatment duration before discontinuation may be confounded by an overrepresentation of long-term responders in the longer-duration groups,” but landmark analyses and multivariable Cox regression models were used to “help reduce potential biases and enhance the reliability of the findings.”

The study investigators reflected on the clinical implications of these results, explaining that although “discontinuation is clearly warranted in cases of severe irAEs,” the management of grade 2 irAEs “often presents a more nuanced challenge for clinicians” and that the findings of this study may help clinicians “provide patients with a clearer, more individualized assessment of their risk of disease progression.” For example, clinicians can take into account factors such as the patient’s duration of treatment with immune checkpoint inhibitors before discontinuation, the response to therapy, and other clinicopathologic characteristics.

“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,” Dr.Pecci said. “Our study can serve as a valuable resource to support clinicians in the complex considerations of treatment discontinuation for irAEs.”

Source:

American Association for Cancer Research. Some patients may experience durable disease control even after discontinuing immune checkpoint inhibitors for side effects. https://www.aacr.org/about-the-aacr/newsroom/news-releases/some-patients-may-experience-durable-disease-control-even-after-discontinuing-immune-checkpoint-inhibitors-for-side-effects/. April 18, 2025.