WINSTON-SALEM, NC – Do small-cell lung cancer patients live longer when they have side effects from immunotherapy? A new study examined that question.
The focus was on immune-related adverse events (irAEs) in extensive-stage small cell lung cancer (ES-SCLC). Researchers from Wake Forest School of Medicine in Winston-Salem, NC, and the VA Healthcare System in Salisbury, NC, point out that immunotherapy helps the immune system fight cancer, and that side effects, caused by treatment inflammation, have been linked to longer survival in many other cancers.
“Prior research indicates a connection between immune-related adverse events (irAEs) and improved progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer. However, limited data exists for extensive stage small cell lung cancer (ES-SCLC),” according to the study in the journal Immunotherapy.1
The study included all ES-SCLC patients who received at least one dose of an immune checkpoint inhibitor between Jan. 2, 2011, and July 4, 2022, using a large retrospective registry from a single institution.
Results indicate that 23% of the 245 patients with ES-SCLC experienced irAEs, 42.9% of which were high-grade (3-4). High-grade irAEs occurred at a median of 1.2 months (interquartile range [IQR] 0.45-2.5), while low-grade irAE occurred at 2.8 months (1.3-5.2).
The study team noted that progression-free survival was significantly longer among any irAE vs none (HR = 0.49; [95%CI 0.32-0.77]) as was overall survival (HR = 0.49; [95%CI 0.34-0.72]).
“In ES-SCLC patients treated with immunotherapy, those who experienced any irAE demonstrated a two-fold increase in both PFS and OS compared to those without an irAE,’” the authors wrote. “This is consistent with other tumor primaries.”
Here is more information on the findings:
- Patient Characteristics and Incidence of irAEs Most irAEs were low-grade (57%), with thyroiditis being the most common (44%). High-grade irAEs, including pneumonitis and colitis, were less frequent (43%) and occurred earlier (median onset 1.2 months).
- Survival Benefits Associated with irAEs Median OS was 12.2 months for low-grade irAE, 7.3 months for high-grade irAE, and only 5.0 months for those without irAEs.
- Impact of irAE Severity on Outcomes Low-grade irAEs were associated with the most significant survival benefit, with hazard ratios for reduced risk of progression or death at 0.38 (95% CI: 0.23–0.63). High-grade irAEs demonstrated improved median survival compared to no irAEs but were not statistically significant due to limited sample size and potential competing risks.
- Clinical Implications for irAE Management High-grade irAEs often result in treatment discontinuation and reduced survival due to their life-threatening nature and inability to re-challenge with immunotherapy. Conversely, low-grade irAEs may allow for continued treatment and contribute to improved outcomes.
- Future Directions and Research Needs This study highlights the need for further investigation into the mechanisms underlying irAEs, particularly in ES-SCLC, and their relationship to survival. Future research should focus on genomics, predictive biomarkers, and treatment optimization, including the role of second-line therapies post-irAE.
- Hunting JC, Price SN, Faucheux AT, Olson E, Elko CA, Quattlebaum A, Ruiz J, Lycan TW Jr. Survival impact of immune-related adverse events in extensive stage small cell lung cancer patients: a retrospective cohort study. 2025 Jan 23:1-6. doi: 10.1080/1750743X.2025.2456448. Epub ahead of print. PMID: 39844686.
