Pembrolizumab and afatinib for recurrent or metastatic head and neck squamous cell carcinoma

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is an important malignancy in Taiwan. Anti-PD-1, including nivolumab or pembrolizumab (pembro), had shown the efficacies against recurrent or metastatic (R/M) HNSCC. Afatinib, an irreversible EGFR tyrosine kinase inhibitor (TKI), had showed its activity against head and neck squamous cell carcinoma. In vitro and animal study showed that afatinib can inhibit macrophage function, increase antigen presentation, and augment the T cell response. The role of afatinib for cancer immunotherapy have not been explored in human. We hypothesized that adding afatinib with pembro may improve the treatment efficacy for patients with R/M HNSCC. Methods: For HNSCC patients who decided to take pembro, the combination with afatinib would be discussed between the physician and the patient. Pembro was planned for 4 cycles. Afatinib was prescribed concurrently with pembro, and will be kept after discontinuation of pembro, until disease progression. For patients taking pembrolizumab and afatinib (P+A), the medical records were reviewed. Patients who have monotherapy with pembrolizumab or afatinib before the P+A were excluded. RECIST 1.1 were used for evaluating tumor response. Results: From Nov. 1, 2016 to Sep. 30, 2017, 41 R/M HNSCC patients (pts) took P+A. The median age was 59 years, and 38 pts were men. The cancer types were: oral cavity: 29 pts, oropharynx: 5 pts, and hypopharynx: 7 pts. The initial treatments were: pembrolizumab 200mg: 27pts; 2mg/kg: 14pts. Eighteen pts are platinum naïve, and 23 pts are platinum refractory. Until Mar. 30, 2018, the median follow-up was 7.6 months. The clinical response was: CR+PR 24/41 (58.5%, 95% CI: 42.8% -74.3%), SD: 9/41, PD: 8/ 41. The median PFS was 7.2 (5.0-9.3) months. The median of OS was not reached. The most common toxicities were: diarrhea 56%, skin rash 44%, mucositis 32%, and handfoot- skin reaction 24%. The incidence of grade 3 or 4 toxicities was 3/41. No pneumonitis were noted in the cohort. Conclusions: The addition of afatinib with pembrolizumab showed good efficacies and tolerable toxicities. Biomarker studies are ongoing. Further confirmatory prospective trial is indicated.