1022PD - Phase II Study of Pemetrexed Plus Cisplatin and Cetuximab in Advanced Squamous Cell Carconima of the Head and Neck

Abstract

ABSTRACT Background Patients (pts) with recurrent or metastatic SCCHN have a very poor prognosis. Platinum-based chemotherapy has long been standard treatment. Adding cetuximab to cisplatin-based combinations has improved overall survival (OS) and is currently standard treatment in SCCHN. In a phase III study, pemetrexed has shown benefit in SCCHN, particularly in performance status (PS) 0-1 pts. Patients and methods Pts who had no more than 1 prior systemic therapy for locally-advanced disease received cetuximab 250 mg/m2 (loading dose:400 mg/m2), pemetrexed 500 mg/m2, with vitamin supplementation, and cisplatin 75 mg/m2 day 1, up to 6 cycles. Pts completing at least 4 cycles had the option to receive maintenance with pemetrexed and cetuximab, or monotherapy, if toxicity occurred. Primary objective was progression-free survival (PFS); secondary objectives were OS, overall response rate (ORR) and safety. Sixty-five patients were needed to meet an objective median PFS of 5.5 months (mos.), with 90% power; 2-sided α of 0.05. Results Sixty-six Caucasians (53 male), median age of 62 years (42-87) received at least 1 dose of therapy. Nineteen pts had a PS of 0; 47 pts had a PS of 1. Median cycles received = 5.0 (1-27). Median PFS was 4.4 mos. (95% CI: 3.6, 5.4); median OS was 9.7 mos. (95% CI: 6.5, 13.1). Fifty-eight pts were evaluable for ORR analysis. ORR was 29.3% (95% CI: 18.1, 42.7); 1 complete response (1.7%); 16 partial responses (27.6%); 20 pts had stable disease (34.5%). An exploratory subgroup analysis showed larynx tumor pts had greater improvement in survival than non-larynx pts; median OS = 20.8 mos.(HR = 0.44; 95% CI= 0.20, 0.95); p = 0.032. Drug-related grade 3/4 toxicities included leukopenia (34.8%), neutropenia (33.4%), fatigue (24.2%), anorexia (12.1%) and hypomagnesemia (10.6%). There were 5 drug-related deaths (7.6%) on treatment (respiratory failure = 2; implant site hemorrhage = 1, sepsis = 1; death, not otherwise specified = 1). Conclusions Efficacy results were consistent with current standard treatment for SCCHN, but the pre-specified goal of median PFS of 5.5 mos. was not met. Although toxicities were consistent with the safety profiles of this combination, there were 5 deaths on treatment. Disclosure J.B. Vermorken: Dr. Jan B. Vermorken is a member of an advisory board for Merck-Serono, Amgen, Boehringer-Ingelheim, Genentech and Sanofi-Aventis and has lectured (compensated) for Merck-Serono, Amgen, Bristol-Byers Squibb and Sanofi-Aventis. T.C. Gauler: Dr. Gauler is an Advisory board member and received honoraria from Eli Lilly and Company. J. Stoehlmacher-Williams: Dr. J. Stoehlmacher-Williams received honoraria for an advisory board and presentations, travel support and various translational research grants from Eli Lilly and Company. J.M. Lopez-Picazo: Dr. Lopez-Picazo is an advisory board member for Eli Lilly and Company. O. Hamid: Dr. Hamid is an employee of Eli Lilly and Company and has stock ownership. A.M. Hossain: Anwar Hossain is an employee of Eli Lilly and Company and has stock ownership. T. Burkholder: Tiana Burkholder is an employee of Eli Lilly and Company and has stock ownership. S. Chang: Dr. Chang is an employee of Eli Lilly and Company and has stock ownership. L. Licitra: Dr. Licitra served as an advisory board member and received research sponsorship from Eli Lilly and Company. All other authors have declared no conflicts of interest.