392TiP A prospective phase II study of individualized adjuvant therapy in patients with locally advanced hypopharyngeal cancer after neoadjuvant therapy

Hypopharyngeal cancer is relatively rare, accounting for only 3% of head and neck cancers. A majority of the patients (pts) present at an advanced stage with a 5-year overall survival of 40%. Despite improvement in local regional control with neoadjuvant therapy, distant metastasis led to poor outcomes in hypopharyngeal cancer. Individualized adjuvant therapy based on pathologic complete response (pCR) and CD8+ T cell infiltration may be a promising strategy for pts after neoadjuvant therapy. Thus, we conducted a phase II study (ChiCTR2200055939) to evaluate the efficacy and safety of neoadjuvant and individualized adjuvant therapy and explore the correlation between tertiary lymphoid structures (TLS) and efficacy/immune microenvironment in pts with locally advanced hypopharyngeal cancer. In the prospective, open-label, single-arm phase II study, pts who have histologically or cytologically confirmed stage II-IVa hypopharyngeal cancer without recurrent/metastatic disease, ECOG performance status of 0-1, and predicted survival >3 months are eligible. Pts will intravenously receive 2-cycle neoadjuvant therapy with pembrolizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (100 mg/m2) on day 1 every 3 weeks. Surgical resection will be scheduled within 21-28 days after the final dose of neoadjuvant therapy. If postoperative pathology shows a pCR, pembrolizumab will be given as adjuvant therapy for 15 cycles. Pts with non-pCR but CD8+ cell density increased ≥20% from baseline will receive adjuvant radiotherapy (50-60Gy) plus pembrolizumab for 15 cycles; otherwise, non-pCR pts will withdraw from the study and receive conventional concurrent chemoradiotherapy. The primary endpoint is 12-month recurrence-free survival (RFS). Secondary endpoints are 18- and 24-month RFS, median RFS, pCR rate, and safety. Exploratory endpoints include the correlation between TLS and pathological response/RFS/immune microenvironment (eg, CD8+ cells, B/T lymphocytes). The phase 2 trial is ongoing. ChiCTR220005593p. The Sixth Medical Center of Chinese PLA General Hospital. Wu Jieping Medical Foundation.