Efficacy, safety, and multi-omics analysis of pembrolizumab combined with nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: A single-arm phase 2 study.

Objective: Based on the findings of the KEYNOTE-048 study, pembrolizumab in combination with platinum and fluorouracil is the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The efficacy and safety of pembrolizumab combined with nab-paclitaxel and platinum in such patients remain unexplored.

Methods: This single-arm phase 2 study enrolled patients with R/M HNSCC who received pembrolizumab (200 mg), nab-paclitaxel (260 mg/m²), and either cisplatin (75 mg/m²) or carboplatin [area under the curve (AUC) 5] every 21 d for up to six cycles, followed by pembrolizumab maintenance therapy. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Exploratory multi-omics analyses were conducted.

Results: Between April 23, 2021, and August 20, 2023, a total of 67 patients with R/M HNSCC were enrolled and received the study treatment. By the data cut-off date of March 2, 2024, 62 (92.5%) patients had received cisplatin, while five (7.5%) patients had received carboplatin. The median follow-up duration was 12.7 (range: 2.3-34.8) months. The ORR was 62.7%, and the DCR was 88.1%. The median PFS, DoR, and OS were 9.7, 13.0, and 18.7 months, respectively. The most common grade 3 adverse events (AEs) were leukopenia (22.4%) and neutropenia (28.4%). Genomic alterations correlated with efficacy outcomes, and dynamic changes in 17 plasma proteins were associated with treatment response. Upregulation of serum interferon (IFN)-γ and interleukin (IL) 8 levels was linked to treatment-related AEs.

Conclusions: Pembrolizumab in combination with nab-paclitaxel and platinum demonstrated promising efficacy and a manageable safety profile in patients with R/M HNSCC. Future studies are warranted to confirm these findings.