Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial.

ABSTRACT

BACKGROUND AND PURPOSE: Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT. METHODS: Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC 10 mg/m2; 5FU 400 mg/m2; Pmab 3 mg/kg). The expected CR rate was 80%. RESULTS: Forty-five patients (male 9, female 36; median age 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia 73.4%; neutropenia 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI 53.4-78.2]. Median follow-up was 43.6 months [IC 95% 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI 65.1-89], 62.2% [IC95% 46.5-74.6] and 68.8 % [IC95% 53.1-80.2] respectively. CONCLUSION: Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials. CLINICALTRIALS gov identifier NCT01581840.