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

TL;DR

This study tested a combination of paclitaxel and cetuximab in patients with head and neck cancer who had previously failed pembrolizumab, showing promising results in response rates and survival.

Contribution

The first prospective trial evaluating paclitaxel plus cetuximab after pembrolizumab failure in recurrent/metastatic SCCHN.

Findings

The overall response rate was 43.9% at 12 weeks with a duration of response of 5.7 months.

Median overall survival was 12.2 months and progression-free survival was 5.9 months, exceeding pre-immunotherapy benchmarks.

The regimen was well-tolerated with common side effects including skin rash and polyneuropathy.

Abstract

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 with R/M SCCHN of the oropharynx, hypopharynx, larynx, or oral cavity, progressing after first-line pembrolizumab-based regimens, received paclitaxel (PTX) 175 mg/m2 every 21 days plus weekly cetuximab (C) 250 mg/m2 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.

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%).

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.

•PaceAce is the first prospective trial testing PTX–C after first-line P failure in R/M SCCHN.•PTX plus C achieved an ORR of 43.9% at 12 weeks and a DoR of 5.7 months in this setting.•Median OS (12.2 months) and PFS (5.9 months) exceeded historical benchmarks from the pre-immunotherapy era.

PaceAce is the first prospective trial testing PTX–C after first-line P failure in R/M SCCHN.

PTX plus C achieved an ORR of 43.9% at 12 weeks and a DoR of 5.7 months in this setting.

Median OS (12.2 months) and PFS (5.9 months) exceeded historical benchmarks from the pre-immunotherapy era.

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