Alpelisib and Immunotherapy: A Promising Combination for Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck

Abstract

ABSTRACT Background Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3‐kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer. Cases A 69‐year‐old woman with locoregional recurrence of PIK3CA‐mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono‐immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58‐year‐old man with recurrent metastatic PIK3CA‐mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum‐based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation. Conclusion Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting.

Keywords

• alpelisib
• head and neck squamous cell carcinoma
• immunotherapy
• PI3K pathway
• PIK3CA