Paclitaxel plus cetuximab for the treatment of R/M SCCHN after first-line pembrolizumab failure: primary analysis from the PaceAce trial

BACKGROUND: No standard second-line treatment has been established for patients with recurrent or metastatic (R/M) squamous-cell carcinoma of the head and neck (SCCHN) progressing after first-line pembrolizumab-based therapy, representing a critical evidence gap in current clinical practice. PATIENTS AND METHODS: for up to six cycles, followed by C maintenance. The primary endpoint was overall response rate (ORR) at 12 weeks. Secondary endpoints included best overall response (BoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), quality of life, and safety. RESULTS: Fifty-seven patients were enrolled (median age 64 years). Twenty-five patients (43.9%) had a primary tumor in the oropharynx, 17 (29.8%) in the oral cavity, 9 (15.8%) in the hypopharynx, and 6 (10.5%) in the larynx. The ORR was 43.9% [95% confidence interval (CI) 30.7% to 57.6%], the BoR was 47.4% (95% CI 34.0% to 61.0%) with nine (15.8%) complete responses, and the DCR was 71.9% (95% CI 58.5% to 83.0%). DoR was 5.7 months (95% CI 5.1 months-not reached). Median PFS and OS were 5.9 months (95% CI 5.5-8.4 months) and 12.2 months (95% CI 10.5-17.6 months), respectively. Six-month PFS and OS rates were 49.0% and 73.0%, respectively. The most frequent non-hematological treatment-related adverse events were C-associated skin rash (78.9%) and PTX-related polyneuropathy (35.1%). CONCLUSIONS: This is the first prospective trial specifically evaluating PTX plus C after failure of first-line pembrolizumab-based therapy in patients with R/M SCCHN. The observed clinical activity and tolerability support this widely available regimen as a potential standard-of-care option in the absence of randomized evidence in this setting.