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Afatinib and pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma (ALPHA Study): A phase II study with biomarker analysis

Authors :
Huai-Cheng Huang
Yuan-Jing Hong
Ruey-Long Hong
Bin-Chi Liao
Ching-Yi Chan
Hsiang-fong Kao
Tseng-Cheng Chen
Chun-Nan Chen
Yen-Lin Huang
Source :
Journal of Clinical Oncology. 39:6024-6024
Publication Year :
2021
Publisher :
American Society of Clinical Oncology (ASCO), 2021.

Abstract

6024 Background: Epidermal growth factor receptor (EGFR) pathway inhibition may synergize with anti-PD1 activity by inhibiting macrophage function, increasing antigen presentation, and augmenting T cell responses. Afatinib, an irreversible EGFR tyrosine kinase inhibitor (TKI), has been shown to enhance anti-PD1 activity in in vitro and animal studies. We thus hypothesized that adding afatinib to pembrolizumab may improve the treatment outcomes for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Methods: The ALPHA study (NCT03695510) is a single-arm, phase II study with a Simon 2-stage design. Patients with platinum-refractory, recurrent, or metastatic HNSCC are eligible for the study. Afatinib (40mg, oral, daily) and pembrolizumab (200mg, every 3 weeks) are administered to eligible patients. The primary endpoint is the objective response rate (ORR). PD-L1 IHC testing (22C3), comprehensive genomic profiling (CGP, Roche Foundation Medicine One CDx), and targeted multiplexed gene expression profiling (Nanostring nCounter PanCancer Immune Profiling Panel) were applied for biomarker analysis. Results: From JAN 2019 to MAR 2020, 29 patients were enrolled in the study. Age: mean = 53.4 years old; M/F = 27/2. Tumor type: oral cavity: 19; oropharynx: 6, hypopharynx: 2, larynx: 2. PD-L1 TPS > = 50: 7/29 (24.1%), CPS > = 20: 8/29 (27.6%), TMB > 10: 0/25 (0%). The common treatment-related adverse events (AEs; all grades, grade > = 3) were skin rash (22/29, 4/29), diarrhea (17/29, 3/29), paronychia (13/29, 0/29), mucositis (9/29, 1/29), and weight loss (2/29, 0/29). One patient experienced grade 2 pneumonitis. Twelve patients had partial responses to the treatment (12/29, ORR: 41.4%). The data cut-off date was 11FEB2021. The median progression free survival (PFS) was 4.1 (95% confidence interval [CI], 1.9-6.3) months. The median overall survival (OS) was 8.4 (95% CI, 4.1-10.8) months. Patients with high PD-L1 expression had a higher response rate (TPS > = 50: ORR = 0.71, CPS > = 20: ORR = 0.63). EGFR amplification might also predict a higher response rate (ORR: 3/3, 100%). MTAP loss or mutation may predict a poor response to the treatment (ORR: 0/5, 0%), shorter PFS (HR: 4.21, [95% CI: 1.34-13.24], p = 0.014), and shorter OS (HR: 4.20 [95% CI: 1.32-13.41], p = 0.015). Nine patients underwent paired pre-treatment and post-treatment biopsies for gene expression analysis. The mRNA of HLA-A, HLA-B, CXCL13, CXCL9, and CD8A were elevated in the post-treatment biopsies. Three patients underwent post-progression biopsies for CGP study. One patient had a new MTAP mutation. Conclusions: Afatinib can modify tumor microenvironment and increase the clinical response rate in pembrolizumab-based therapy in HNSCC patients. PD-L1, EGFR amplification, and MTAP loss/mutation could be biomarkers for cancer immunotherapy. Clinical trial information: NCT03695510.

Details

ISSN :
15277755 and 0732183X
Volume :
39
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........96bc738074db29da34513b28ae7d75a3