1016O - Phase 2, Randomized Trial (CONCERT-2) of Panitumumab (PMAB) Plus Radiotherapy (PRT) Compared with Chemoradiotherapy (CRT) in Patients (PTS) with Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LASCCHN)

Abstract

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.