The following is a summary of “Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma,” published in the September 2023 issue of Oncology by Keam, et al.

An oncologic approach tailored to head and neck squamous cell carcinoma (HNSCC) is imperative. For a study, researchers sought to conduct a genomic profile-based umbrella trial targeting patients with platinum-refractory recurrent and/or metastatic HNSCC.

In the multicenter, open-label, single-arm phase II trial, targeted next-generation sequencing (NGS) was performed. Patients were allocated to treatment arms based on their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, a fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. Patients without a matching target were assigned to arm 5, duvalumab ± tremelimumab, an anti–PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. Cross-over to arm 5 was allowed upon progressive disease (PD) in arms 1-4. The primary endpoints were disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment.

From October 2017 to August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2%, and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In cases of PD with durvalumab, tremelimumab was added, resulting in an ORR of 2.2% for durvalumab + tremelimumab. Median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. Median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, manageable toxicity profiles were observed, with no treatment-related deaths.

The study represented the first biomarker-driven umbrella trial for platinum-refractory HNSCC utilizing matched molecular targeted agents. NGS-based genomic phenotyping was found to be both methodologically feasible and applicable.

Reference: ascopubs.org/doi/10.1200/JCO.22.02786