Neoadjuvant chemoimmunotherapy with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-2): An open-label, single-arm, phase 2 study.

6069 Background: Neoadjuvant chemoimmunotherapy has been an emerging hotspot for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but the treatment response still requires improvement. Given the potential synergistic antitumor effects of dual inhibition of the PD-1/L1 and EGFR pathways, we proposed a novel neoadjuvant treatment regimen combining chemoimmunotherapy with EGFR-TKI, followed by adjuvant immunotherapy treatment, and evaluated the efficacy and safety of this approach. Methods: This open-label, single-arm, phase 2 trial was done at a tertiary hospital in China. Patients were eligible if they were aged at least 18 years old; had pathologically confirmed HNSCC with locally advanced disease according to the AJCC 8th Edition; had an ECOG performance status of 0−1; had at least one measurable target lesion according to RECIST 1.1 criteria; and had sufficient organ function. Patients with LA-HNSCC received two cycles of tislelizumab (200mg) and TP (nab-paclitaxel and cisplatin) chemotherapy, administrated on day one of each three-week cycle, along with afatinib (30mg) during the intermittent period between chemoimmunotherapy cycles, followed by 15 cycles of adjuvant tislelizumab treatment. The primary endpoint was the complete pathologic response (pCR) rate, defined as the percentage of patients with no detectable RVT cells in the resected primary tumor. Results: A total of 40 patients were enrolled and received neoadjuvant treatment, 32 of whom proceeded to surgical resection and achieved a pCR rate of 40.6% (95% CI: 23.7−59.4%). The overall response rate (ORR) was 82.5% (95% CI: 67.2−92.7%). The median follow-up time was 14.4 months (range: 2.4−27.6 months) . The estimated 1-year overall survival (OS) was 96.7% (95%CI: 90.5%−100%). No deaths occurred among patients who achieved pCR/MPR. The most common treatment-related adverse events (TRAEs) of any grade were alopecia (100%), followed by nausea (62.5%), lymphopenia (57.5%), diarrhea (55%), and rash (55%). The most common TRAE of grade 3−4 was lymphopenia (5/40, 12.5%). No treatment-related surgical delays were observed. Neoadjuvant treatment induced a significant increase in the proportion of peripheral CD8+ T cells, along with a reduction in B cells. TP53 wild-type patients were more likely to achieve a more favorable pathologic response compared to those with a TP53 mutation. A significant difference in oral microbial composition was found between patients with different pathologic responses. Conclusions: This study firstly reported the promising efficacy and acceptable safety profile of neoadjuvant chemoimmunotherapy combined with apatinib in the treatment of patients with LA-HNSCC. Further evaluation in large-scale clinical trials with longer follow-up periods is needed. Clinical trial information: NCT05516589 .