Does Stopping ICI Therapy Affect Survival in HNSCC?

TOPLINE:

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICIs) show comparable survival outcomes whether they continued or discontinued treatment at 1 or 2 years vs continued past those points.

METHODOLOGY:

• Although ICIs are a frontline treatment for patients with recurrent or metastatic HNSCC, questions remain about the optimal duration of therapy, and the advantages and risks of reintroducing ICIs after disease progression. Determining the optimal treatment duration is crucial to prevent overtreatment and reduce the physical and financial burdens of long-term ICI therapy.
• Researchers conducted a retrospective cohort study using the Flatiron Health nationwide oncology database, including 4549 patients with recurrent or metastatic HNSCC treated with ICIs from 2015 to 2023. The cohort’s median age was 66 years, and most of them were men (78.1%), with 66.4% being identified as White individuals.
• The study compared outcomes of patients who discontinued ICI therapy at 1 and 2 years vs those who continued beyond those two points, and assessed outcomes after ICI rechallenge. The immediate rechallenge group restarted ICI treatment after a break of at least 60 days without any non-ICI therapy. The delayed rechallenge group had a non-ICI therapy between their initial and subsequent ICI treatments.
• Researchers analyzed patients’ overall survival (overall survival) from ICI initiation using the Kaplan-Meier method, and Cox multivariable regression examined associations of key variables, such as line of therapy and human papillomavirus status, with survival.

TAKEAWAY:

• Median overall survival was 10.9 months, with longer overall survival observed in patients receiving ICI as frontline therapy (12.2 months) than in those receiving second-line (8.7 months) or third-line (9.1 months) therapy. Patients with human papillomavirus (HPV)-positive cancer had a median overall survival of 16.6 months, while those with HPV-negative cancer had a median overall survival of 8.8 months.
• The median overall survival at one year was 40.7 months for those who discontinued treatment versus 57.7 months for those who continued (hazard ratio [HR], 1.33; 95% CI, 0.84-2.11; P = .22). At two years, the median overall survival for both groups was not reached (HR, 0.52; 95% CI, 0.22-1.22; P = .13).
• Median overall survival was “promising” after ICI rechallenge at 15.7 months in the immediate group and 9.9 months in the delayed rechallenge group with a median time to next treatment of 10.4 and 4.6 months, respectively,

IN PRACTICE:

“Discontinuation of ICI in long-term responders at 1 or 2 years may be a reasonable strategy that does not appear to compromise survival,” the authors concluded. “ICI rechallenge can provide meaningful clinical benefit in some patients.”

SOURCE:

The study was led by Lova Sun, MD, MSCE, Perelman School of Medicine, University of Pennsylvania in Philadelphia. It was published online on August 19 in JAMA Network Open.

LIMITATIONS:

A major limitation of this analysis is that the reasons for ICI discontinuation and restarting were not documented. Rechallenge may have occurred due to disease progression or recovery from side effects. Additionally, since this study was conducted using a United States-based observational database, findings are not completely generalizable to a global population.

DISCLOSURES:

Sun disclosed receiving clinical trial funding from Blueprint, Seagen, IO Biotech, Erasca, Immunocore, and Abbvie. Jonathan D. Schoenfeld, MD, reported grants from Merck, personal fees from EMD Serono, Merck KGA, Immunitas, Debiopharm, Bristol Myers Squibb, Regeneron, EMD Serono, LEK, ACI Clinical, Astellas, Stimit, Genentech, SIRPant, and Castle Biosciences. Glenn J. Hanna, MD, disclosed grant funding, consulting/advisory, and research support from Merck. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.