Single-center phase 2 trial of neoadjuvant chemoimmunotherapy with afatinib for locally advanced head and neck squamous cell carcinoma

While immune checkpoint inhibitor-based neoadjuvant therapy shows promise in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), the optimal regimen has yet to be established. The phase 2 neoCHANCE-2 trial at Sichuan University (Chengdu, China) evaluated neodadjuvant combination of chemotherapy with dual blockade of PD-1 and EGFR in LA-HNSCC. A total pf 40 patients were enrolled and received two cycles of neoadjuvant tislelizumab and TP chemotherapy (nab-paclitaxel and cisplatin), administered on day 1 of each 21-day cycle, along with afatinib during the interval between chemoimmunotherapy cycles, followed by surgical resection. The primary endpoint was complete pathological response (pCR) rate. Among 32 patients who proceeded to surgical resection, the pCR rate was 40.6% (95% CI 23.7-59.4), while the objective response rate was 82.5% (67.2-92.7). The 1-year overall survival rate was 97.3% (95% CI 92.2-100). The most common grade 3 or 4 treatment-related adverse event was lymphopenia, in 5 of 40 patients (12.5%); there were no grade 5 TRAEs and treatment-related surgical delays. In prespecified biomarker analyses, increased cytotoxic T lymphocytes and B cells in the tumor immune microenvironment were associated with response. Neoadjuvant treatment induced a significant increase in the proportion of peripheral CD8+ T cells, along with a reduction in B cells. The authors conclude that the neoadjuvant combination of chemoimmunotherapy plus afatinib had promising efficacy an acceptable safety in patients with LA-HNSCC.