Concurrent immunotherapy and radiation in cisplatin-ineligible patients with HNSCC: a systematic review & meta-analysis

BACKGROUND: Head and squamous cell carcinoma (HNSCC) in the locally advanced setting is challenging to treat and remains an area of significant morbidity and mortality. For patients who are cisplatin-ineligible and considered unresectable, there is no clear standard of care including the choice of radiosensitizer. METHODS: OVID Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched. Randomized clinical trials (RCTs) of cisplatin-ineligible unresectable HNSCC patients who were randomized to an immune checkpoint inhibitor concurrent with radiation compared to a control arm were included. Data was pooled and assessed using a random-effects model for the meta-analysis. RESULTS: Three eligible RCTs were identified and analyzed which comprised 594 patients whose median age ranged from 65-72 years. There was no difference in overall survival (pooled HR 1.02, 95% CI 0.76-1.37, p = 0.88) or PFS (pooled HR 0.92, 95% CI 0.68-1.23, p = 0.56). Grade greater than or equal to 3 adverse events were favored to be less in the immunotherapy arm. CONCLUSIONS AND RELEVANCE: Immune-checkpoint inhibitors are not superior to cetuximab when used with definitive radiation in HNSCC. Further study is warranted, given its potential signal for non-inferior survival with less toxicity profile trends.