Neoadjuvant immunochemotherapy for locally advanced hypopharyngeal squamous cell carcinoma: Pooled results analysis from two prospective single-arm phase 2 trials.

6078 Background: Hypopharyngeal squamous cell carcinoma (HPSCC) suffered poorest prognosis among various head and neck lesions. The efficacy, safety, and biomarkers of immunochemotherapy as neoadjuvant treatment for locally advanced HPSCC deserves further investigation. Methods: This study enrolled untreated (AJCC 8th ) stage III-IV HPSCC patients (pts) from two phase 2 trials (ChiCTR2200060094; ChiCTR2200055719). The treatment regimen involved PD-1 inhibitors plus taxanes and platinum-based chemotherapy for two cycles. A multi-disciplined team consultation determined either surgery or chemoradiotherapy. The primary endpoint was ORR and pCR. Second endpoints included DCR, PFS, OS, and safety. Biomarker analysis mainly via plasma Olink proteomics assay. Results: From June 9, 2021 to December 5, 2023, 68 pts received treatment and 30 pts underwent surgery. The baseline characteristics were shown in the table. Most AEs were grade 1-2, and the incidence of grade 3 AEs was 30.9%, mainly neutropenia (20.6%). The ORR, DCR were 63.2% (43/68) and 100% (68/68). Imaging results showed that 38.2% (26/68) of patients were assessed as depth partial response (shrinkage ≥ 50%) after neoadjuvant treatment. Among 30 patients who underwent surgery, pCR reached 23.3% (7/30), two pts with CT/MRI assessed SD were ultimately confirmed pCR. Median follow-up was10.5 months, the median PFSand OS were not reached. The 1 year-PFS and OS rates were 74.2% and 86%. The 1 year- laryngeal function preservation rate was 93.9%. 22 pts with baseline plasma samples were included in the analysis of serum proteome biomarkers. The plasma protein expression of GZMH, GZMA, KLRD1, IL12RB1, CD244, NCR1, CXCL10, CXCL13, LAG3, IL10, MCP-3, CCL20, CD8A, TWEAK, and HGF at baseline was significantly lower in pts with tumor shrinkage≥50% which suggested the potential of these biomarkers in predicting treatment response. Conclusions: PD-1 inhibitors combined with taxanes and platinum-based chemotherapy are well tolerated and effective in the neoadjuvant treatment of locally advanced HPSCC. The discordance between radiological and pathological assessments after neoadjuvant immunotherapy deserves further exploration, which requires a more precise method to screen the appropriate treatment population. Alterations in plasma proteins may be promising biomarkers for predicting treatment response in the future. Clinical trial information: ChiCTR2200060094; ChiCTR2200055719. Baseline characteristics of pts. Overall (N=68) Age Median range 58.0 42.0, 74.0 Stage III 8 (11.8%) IV 60 (88.2%) PD-L1 CPS =20 24 (35.3%) unknown 6 (8.8%) TMB =10 5 (7.4%) unknown 29 (42.6%) Following therapy Surgery 30 (44.1%) Not surgery 38 (55.9%) PD-1 Pembrolizumab 47 (69.1%) Tislelizumab 21 (30.9%) PD-L1: programmed death-ligand 1; CPS: combined positive score.