880P - Paclitaxel plus cetuximab for the treatment of recurrent and/or metastatic head and neck cancer after first-line checkpoint inhibitor failure: Primary analysis from the pace ace trial

Background

Defining optimal second-line treatment for patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression during immunotherapy with standard-of-care pembrolizumab-based regimens represents an important unmet clinical need. We, therefore conducted this prospective multi-center international phase II trial to investigate the efficacy of paclitaxel (PTX) plus cetuximab (C) in this specific patient population.

Methods

Patients with R/M SCCHN of the oropharynx, hypopharynx, larynx, or oral cavity, who failed prior pembrolizumab based first line therapy, were included. Patients received PTX 175mg/m², q21 plus C 250mg/m² weekly for up to six cycles, followed by C maintenance therapy. The primary endpoint was overall response rate (ORR). Patients were monitored for response every 12 weeks employing RECIST 1.1 criteria. Secondary endpoints comprised disease control rate (DCR), overall survival (OS), progression free survival (PFS) duration of response (DOR), quality of life and safety.

Results

Fifty-seven patients were enrolled. The median age was 64 (range: 28-81) 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 majority of oropharyngeal carcinoma patients were p16 negative (56%). The ORR was 47.4% (95% CI 34.0%-61.0%) with 8 (14.0%) complete responses achieved. Median duration of response was 5.5 months (95% CI 3.3-∞). Disease control occurred in 42 patients resulting in a DCR of 71.9% (95% CI 58.5%-83.0%). The median PFS was 5.9 months (95% CI 5.4-8.2), and the median OS 14.0 months (95% CI 10.8-20.5). The 6-months PFS and OS rates were 48% and 74%, respectively. The most frequent non-hematological treatment related adverse events (AE) comprised cetuximab associated skin rash, reported in 45 patients (78.9%), and paclitaxel related polyneuropathy, which occurred in 20 patients (35.1%).

Conclusions

PTX in combination with C is effective and safe in R/M SCCHN patients after first line pembrolizumab failure and represents a potential treatment option in this setting.

Clinical trial identification

NCT04278092 EudraCT 2019-003114-13.

Editorial acknowledgement

Legal entity responsible for the study

Medical University of Vienna.

Funding

Merck KGaA.

Disclosure

T. Fuereder: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Merck KGaA, Invios, Takeda, Pfizer, Janssen, Amgen, Roche, Boehringer Ingelheim RCV; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eli Lilly, Sanofi; Financial Interests, Institutional, Funding: Merck Sharp & Dohme, Merck KGaA, Bristol Myers Squibb, Amgen, Roche. K. Klinghammer: Financial Interests, Personal, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: Merck Sanofi, Onkowissen, Biontech; Non-Financial Interests, Principal Investigator: AstraZeneca, GSK, Kura Oncol, MSD, Biontech; Non-Financial Interests, Advisory Board: DGHO, DKG, AIO. D.A. Hahn: Financial Interests, Personal, Advisory Board, advisory board head and neck cancer: BMS, MSD; Financial Interests, Personal, Advisory Board, advisory board head and neck cancer, invited speaker: Merck. B. Grünberger: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Taiho. F. Kocher: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Merck KGaA. G. Gamerith: Financial Interests, Personal, Advisory Role, Travel Grants: Merck KGaA. C. Wagner, L. Berchtold: Financial Interests, Institutional, Funding: Merck KGaA. M. Burian: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Merck KGaA. All other authors have declared no conflicts of interest.