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

•This phase II trial studied the tolerance and complete response rate at 8 weeks of panitumumab combined with MMC-5FU-based chemoradiotherapy for locally advanced anal cancers.•Panitumumab in combination with chemoradiotherapy failed to meet the expected complete response rate (80%).•Disease-free survival at 3 years was 62.2% [IC95%: 46.5–74.6], similar to usual DFS with standard CRT for locally advanced anal cancers.•The association exhibited a poor tolerance despite reduced doses of 5FU and panitumumab defined in a previous phase 1 study. 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. 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%. 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. 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.