911P - Association of genomic landscape and plasma protein dynamic changes with clinical outcome in patients with R/M HNSCC treated with pembrolizumab with nab-paclitaxel and platinum

Background

The predictive effects of immunotherapy biomarkers are still limited in clinical practice. We evaluated the tumor genomic landscape and dynamic changes in plasma circulating biomarkers in R/M HNSCC pts receiving immunochemotherapy.

Methods

The clinical data were obtained from R/M HNSCC pts treated with pembrolizumab, nab-paclitaxel and platinum from the phase II clinical trial (NCT04857164). Tissue and blood specimens were collected for multi-omics analyses, including immunohistochemistry, high-resolution sequencing based on probe capture, and Olink target 92 Immuno-oncology panel on plasma proteins.

Results

Between April 23^rd, 2021, and August 20^th, 2023, a total of 67 R/M HNSCC pts were enrolled, 46 pts and 22 pts had sequencing and Olink results, respectively. In all pts group, the ORR was 62.7%, and the mPFS and mOS were 11.6(95%CI:8.29-12.94) months and 18.7(95%CI:10.57-26.90) months, respectively. The patients with genomic amplification in 11q13 region (including CCND1[ORR 29% vs. 69%], FGF19[ORR 22% vs. 73%], FGF3[ORR 33% vs. 70%], and FGF4 [ORR 29% vs. 69%]) had poor responses to pembrolizumab, nab-paclitaxel and platinum. TERT (HR,3.87[95%CI:1.53-9.74], P=0.004) and PIK3CA (HR,3.21[95%CI:1.17-8.84], P=0.024) mutations were significantly related to poor PFS, while CDKN2A mutations were associated with poor OS (HR,3.75[95%CI:1.24-11.31], P=0.019). Comparing with baseline status, 17 protein expression levels (ANGPT1, ANGPT2, CCL23, CD8A, CD40-L, CSF-1, EGF, GZMH, IL7, IL10, MCP-2, MMP7, MMP12, NCR1, PDCD1, PDGF subunit B, and VEGFA) were elevated, and 1 protein expression level (CASP-8) was decreased in serum after 2 cycles of treatment in pts with either poor efficacy or inferior survival. Upregulation of serum IFN-γ and IL8 was significantly associated with the occurrence of most TRAEs, such as fatigue, hyper/hypothyroidism, and rash.

Conclusions

The genomic alterations and dynamic changes of plasma circulating proteins were highly correlated, suggesting their possible value as a predictive marker for efficacy and safety in R/M HNSCC pts treated with pembrolizumab, nab-paclitaxel, and platinum. Future studies are needed.

Clinical trial identification

NCT04857164.

Editorial acknowledgement

Funding

1. Beijing Hope Run Special Fund of Cancer Foundation of China (LC2022A30) 2. Major Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MOMP 2022010).

Disclosure

All authors have declared no conflicts of interest.