1016O - Phase 2, randomized trial (CONCERT-2) of panitumumab (PMAB) plus radiotherapy (PRT) compared with chemoradiotherapy (CRT) in patients (pts) with unr...

Date 01 October 2012
Event ESMO Congress 2012
Session Head and neck cancer
Topics Anti-Cancer Agents & Biologic Therapy
Head and Neck Cancers
Surgery and/or Radiotherapy of Cancer
Presenter Jordi Giralt
Authors J. Giralt1, J.M. Trigo2, S. Nuyts3, E.M. Ozsahin4, K. Skladowski5, G. Hatoum6, J. Daisne7, A. Zhang8, K.S. Oliner9, A. VanderWalde10
  • 1Vall d`Hebron University Hospital, Barcelona/ES
  • 2Medical Oncology, Hospital Universitario Virgen de la Victoria, Malaga/ES
  • 3Radiation Oncology, University Hospitals Leuven, Leuven/BE
  • 4Radiation Oncology, Lausanne University Medical Center (Centre Hospitalier Universitaire Vaudois), Lausanne/CH
  • 5Radiation Oncology, Centrum Onkologii Instytut M. Sklodowskiej-Curie, Gliwice/PL
  • 6Clinical Biomedical Sciences, Florida Atlantic University, Lake Worth/US
  • 7Radiation Oncology, Clinique & Maternité Ste-Elisabeth, Namur/BE
  • 8Global Biostatistics, Amgen, Thousand Oaks/US
  • 9Medical Sciences - Ivd, Amgen, Thousand Oaks/US
  • 10Oncology Therapeutics, Amgen, Thousand Oaks/US

Abstract

Background

We evaluated the safety and efficacy of pmab, a fully human monoclonal antibody against the epidermal growth factor receptor, by comparing PRT with CRT in pts with LASCCHN.

Methods

Pts with stage III, IVA, or IVB previously untreated LASCCHN of all sites excluding the nasopharynx were randomized 2:3 to open-label CRT or PRT. CRT included 2 cycles of cisplatin 100 mg/m2 during accelerated fractionation radiotherapy (XRT; 70-72 Gy over 6-6.5 weeks). Pmab included 3 cycles at a dose of 9.0 mg/kg with each cycle administered with XRT. This was an estimation study with no formal hypothesis testing. The primary endpoint was locoregional control (LRC) rate at 2 years; key secondary endpoints were progression free survival (PFS), overall survival (OS), and safety. Preplanned HPV subset analysis (determined by p16 immunohistochemistry) was performed on available samples.

Results

Of 151 treated pts (90 PRT, 61 CRT), 84% were men; median age was 58 years; ECOG PS 0: 64%. Overall, the 2-year LRC rate (95% CI) was 51% (40%-62%) for PRT and 61% (47%-72%) for CRT. For both PFS (hazard ratio [HR] = 1.73 [95% CI: 1.07-2.81]; p = 0.03) and OS (HR = 1.59 [95% Cl: 0.91-2.79]; p = 0.10), outcomes favored the CRT arm. Of 99 pts with tumors evaluable for HPV, 24% were HPV+. In 75 HPV- tumors, a difference was observed in PFS (HR = 2.04 [95% Cl: 1.05-3.96]; p = 0.04), with trends also favoring CRT in LRC and OS. Overall, dose intensity was high for all components of therapy in both arms (median relative dose intensity: 100% for pmab and 99% for cisplatin, median XRT dose: 100% in both arms). Grade 3+ adverse events (AEs) occurred in 85% PRT vs 81% CRT pts. Key differences in grade 3+ toxicity between arms (PRT, CRT) included skin disorders (which is a composite of skin-related AEs) (35%, 3%), neutropenia (0%, 13%), and febrile neutropenia (0%, 8%).

Conclusions

Trends favored the CRT arm for the primary endpoint (LRC at 2 years), as well as other measures of efficacy, in this predominantly HPV- LASCCHN population. Small numbers limit conclusions in the HPV+ group. Both PRT and CRT appeared well tolerated.

Disclosure

G. Hatoum: Advisory Board Member for Amgen

K. Oliner: Amgen stock

A. Vanderwalde: Corporate-sponsored research (Amgen), full-time employee of Amgen

All other authors have declared no conflicts of interest.