In a study reported in JAMA Network Open, Sun et al analyzed survival outcomes with immune checkpoint inhibitor (ICI) treatment used in first- or second-line therapy, with treatment continuation vs discontinuation, and with treatment rechallenge in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Study Details
The U.S. retrospective cohort study used data from the Flatiron Health nationwide oncology database on patients treated with ICIs for recurrent or metastatic HNSCC from 2015 to 2023. Overall survival was analyzed according to first- or second-line of treatment, treatment discontinuation after 1 or 2 years in long-term responders, and rechallenge with ICI after a ≥ 60-day period off ICI therapy without intervening systemic treatment (immediate rechallenge) or with intervening systemic treatment (delayed rechallenge).
Key Findings
The cohort consisted of 4,549 patients with recurrent or metastatic HNSCC who received ICI-containing therapy. A total of 3,000 patients (65.9%) received ICI in first-line therapy and 1,207 (26.5%) in ICI in second-therapy.
In the total cohort, median overall survival from start of ICI treatment was 10.9 months (interquartile range [IQR] = 4.1–29.1 months). Median overall survival was longer among patients who received first-line vs second-line therapy (12.2 months [IQR = 4.8–32.0 months] vs 8.7 months [IQR =3.2–22.4 months]), those with human papillomavirus (HPV)-positive vs HPV-negative cancer (16.6 months [IQR = 6.5–43.9 months] vs 8.8 months [IQR = 3.5–24.0 months]), and those with an Eastern Cooperative Oncology Group performance status of 0 or 1 vs ≥ 2 (13.5 months [IQR = 5.2–33.9 months] vs 5.5 months [IQR = 2.0–13.7 months]).
A total of 43 patients stopped and 577 continued ICI treatment at 1 year in the absence of next treatment or death; 47 discontinued and 183 continued treatment at 2 years. Median overall survival among patients who discontinued vs continued treatment at 1 year was 40.7 vs 57.7 months (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 0.84–2.11, P = .22). Median overall survival among patients who discontinued vs continued treatment at 2 years was not reached vs not reached (HR = 0.52, 95% CI = 0.22–1.22, P = .13).
Median overall survival after ICI rechallenge was 15.7 months (IQR = 13.7–21.9 months) in patients with immediate rechallenge and 9.9 months (IQR = 3.7–18.1 months) in patients with delayed rechallenge.
The investigators concluded, “In this large cohort study of patients with recurrent or metastatic HNSCC receiving ICI-based therapy, survival estimates closely mirrored clinical trial results, both in frontline and later-line settings. Discontinuation of ICI in long-term responders at 1 or 2 years may be a reasonable strategy that does not appear to compromise survival. ICI rechallenge was associated with clinical benefit in a subset of patients.”
Lova Sun, MD, MSCE, of the Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
