1022PD - Phase II study of pemetrexed plus cisplatin and cetuximab in advanced squamous cell carconima of the head and neck

Date 30 September 2012
Event ESMO Congress 2012
Session Head and neck cancer
Topics Cytotoxic agents
Head and Neck Cancers
Biological therapy
Presenter Jan B. Vermorken
Authors J.B. Vermorken1, T.C. Gauler2, J. Stoehlmacher-Williams3, A. Dietz4, J.M. Lopez-Picazo5, O. Hamid6, A. Hossain6, T. Burkholder6, S. Chang6, L. Licitra7
  • 1Department Of Oncology, U.Z.A. University Hospital Antwerp, 2650 - Edegem/BE
  • 2Dept. Of Medicine (cancer Research), University Hospital, 45122 - Essen/DE
  • 3Oncology, University Hospital Dresden, Dresden/DE
  • 4Oncology, Universitatsklinikum Leipzig, 04103 - Leipzig/DE
  • 5Oncology, Clinica Universidad de Navarra, Pamplona/ES
  • 6Oncology, Eli Lilly and Company, Indianapolis/US
  • 7Oncology, Instituto Nazionale Tumori, Milan/IT




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.


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).


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.


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.