910P - Multi-omics analysis of tislelizumab plus nab-paclitaxel and cisplatin as neoadjuvant immunochemotherapy for locally advanced hypopharyngeal squamous cell carcinoma: A prospective single-arm phase II trial

Background

Hypopharyngeal squamous cell carcinoma (HPSCC) suffers poorest prognosis among head and neck subtypes. The efficacy, safety, and biomarkers of neoadjuvant immunochemotherapy for HPSCC warrant further investigation.

Methods

This prospective phase II trial enrolled untreated locally advanced HPSCC pts and utilized tislelizumab plus nab-paclitaxel and cisplatin as neoadjuvant therapy. The primary endpoints were ORR and pCRR. The secondary endpoints were DCR, PFS, OS, DFS, and safety. PD-L1 expression was evaluated through IHC. Genomic alteration was detected via targeted sequencing. Plasma biomarker analysis was performed using Olink proteomics assay.

Results

From May 2022 to Nov 2023, 45 pts were included. The ORR, DCR, and pCRR were 62.2%, 100%, and 21.4%. Two pts with radiological SD were ultimately confirmed pCR. With a median follow-up of 11.6 months, the median PFS, DFS, and OS were not reached. The 12-month PFS, DFS, and OS rates were 69.8%, 81.6%, and 77.4%. The 12-month larynx preservation rate was 91.9%. AEs were mostly G1-2, with a 31% incidence of ≥G3 AEs, primarily neutropenia (18%). Pts who had undergone surgery had significantly better PFS (HR=0.24, P=0.03) and OS (HR=0.21, P=0.04) compared to others. Pts with PD-L1 CPS≥5 had significantly better PFS (HR=0.20, P=0.03) and OS (HR=0.09, P<0.01) than those with PD-L1 CPS<5. Genomic alteration was not associated with tumor response or survival. Olink proteomics assay revealed that baseline protein levels of GZMH, GZMA, KLRD1, IL12RB1, CD244, NCR1, CXCL10, CXCL13, LAG3, IL10, MCP-3, CCL20, CD8A, and TWEAK were significantly higher in pts with tumor shrinkage of <50% compared to those with tumor shrinkage of ≥50%.

Conclusions

Tislelizumab plus nab-paclitaxel and cisplatin as neoadjuvant therapy demonstrated manageable safety and promising efficacy in HPSCC. Pts with radical surgery achieved PFS and OS benefit. PD-L1 CPS≥5 is an indicator for better PFS and OS. The discordance between radiological and pathological assessments deserves further exploration. Plasma proteins show promising predictive value for predicting the deep response to immunochemotherapy in HPSCC.

Clinical trial identification

ChiCTR2200060094.

Editorial acknowledgement

Legal entity responsible for the study

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.