Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) historically has had a poor prognosis, with limited effective treatment options for patients who have experienced disease progression while receiving platinum-based chemotherapy. Over the past several years, checkpoint inhibitors (CPIs) with or without chemotherapy have been shown to be associated with favorable outcomes compared with traditional cytotoxic chemotherapy and are now a part of the standard of care for patients with recurrent or metastatic HNSCC. However, response rates remain low, CPI therapy does not benefit most patients, and questions remain regarding the optimal clinical selection and sequencing of immunotherapy in various subsets of patients with head and neck cancer.

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There are limited data on outcomes among patients with recurrent or metastatic HNSCC treated with CPI outside a clinical trial setting. In this cohort study, authors Sara B. Hobday et al examined response rates, survival outcomes, and associations with key clinical covariates in a large, contemporary cohort of patients with recurrent or metastatic HNSCC treated with CPIs with or without chemotherapy.
This retrospective cohort study included patients older than 18 years who received CPI-based therapy for recurrent or metastatic HNSCC at the University of Pennsylvania from January 1, 2015, through August 15, 2021. Clinical and survival data were abstracted through medical record review. The main outcomes were overall survival, progression-free survival, and response rates.
The study cohort consisted of 212 patients, of whom 165 (77.8%) were male, 148 (69.8%) were former or current smokers, and 66 (31.1%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater; median age was 63.2 years (IQR, 57.2-71.2 years).
Primary tumor sites included the oropharynx (99 [46.7%]), oral cavity (61 [28.8%]), and larynx or hypopharynx (52 [24.5%]). Most (126 [59.4%]) received CPI as first-line systemic therapy, and 23 (10.8%) received combination CPI with chemotherapy.
The overall response rate was 30.1%.
Estimated 1-year overall survival was 51.8% (95% CI, 44.5%-58.8%), and estimated 1-year progression-free survival was 9.4% (95% CI, 5.0%-15.5%).
Median overall survival was 12.9 months (IQR, 4.1-36.5 months), and median progression-free survival was 3.9 months (IQR, 1.9-17.8 months).
Non–oral cavity primary site (vs oral cavity) was associated with improved overall survival (human papillomavirus–positive oropharynx: hazard ratio [HR 0.567]; all other sites: (HR, 0.491), and T category of 4 at presentation (HR, 1.594) and an ECOG performance status greater than 1 (HR, 2.720) were associated with worse overall survival.
In this large cohort study of patients with recurrent or metastatic mucosal HNSCC from the general population who were treated with CPIs, the observed survival and response rates were similar to those observed in previous clinical trials despite 31.1% of patients having an ECOG performance status of 2 or greater. Patients with oral cavity cancer had inferior OS compared with patients with HNSCC at all other subsites. Study findings support the use of CPI therapies for first- or second-line treatment of recurrent or metastatic HNSCC.
Source: Sara B. Hobday, BA; Robert M. Brody, MD; Barry Kriegsman, MD, PhD; JAMA Otolaryngology–Head & Neck Surgery
doi:10.1001/jamaoto.2022.2284