Phase II Study of Panitumumab, 5-Fluorouracil, Mitomycin-C and Radiotherapy Treatment in Patients with Non-Metastatic Squamous Cell Carcinoma of the Anal Canal: Safety and Efficacy Results (VITAL Study)—gemcad 09-02.

3566 Background: More than 80% of squamous cell carcinoma of the anal canal (SCCAC) express epidermal growth factor receptor protein (EGFR). VITAL was a phase II, multicentre, single arm study, which aimed to evaluate efficacy and safety of the addition of panitumumab (Pmab) to fluorouracil (5-FU), mitomycin C (M) and radiotherapy (RT) standard treatment in patients with SCCAC (NCT01285778). Methods: Treatment naïve patients ≥ 18 years old, with SCCAC (Stage T2-T4, any N, M0 defined by MRI) with ≤ 2 ECOG performance status, received Pmab (6 mg/kg, day 1 and q2w during 8 weeks), 5-FU (1000 mg/m2/day; IV infusion, days 1-4 and 29-32) and M (10mg/m2, days 1 and 29) plus RT 45 Gy (1.8 Gy/fraction) to the primary tumour and mesorectal, iliac and inguinal lymph nodes, plus boost dose of 10-15 Gy to primary tumour and affected lymph nodes. The primary objective was disease free survival (DFS) at 3 years (anticipated DFS: 73.7% ± 12%) estimated by Kaplan-Meier. Multivariable analysis of efficacy variables adjusting for key baseline covariates will be presented. Results: A total of 58 patients (31 women; median age: 59 years; ECOG performance status: 0 [41%] / 1 [57%] / 2 [2%]; TNM II [29%] / IIIA [21%] / IIIB [47%]/ non-evaluable [NE] [4%]) were evaluated. The 3-year DFS rate was 61.1% (95%CI 47.1 - 72.4). The median follow-up was 45 months. The 3-year overall survival rate and progression free survival rate were 78.4% (95%CI 65.1-87.1) and 57.5% (95%CI 43.6 - 69.2) respectively. Eighteen patients (31.0%) had a colostomy within the first 2 years post-treatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Radiation skin injury (19%), diarrhoea (10%), neutropenia (9%) and leukopenia (19%) were the most common ( > 10%) grade 3-4 adverse events associated with Pmab. There were no toxic deaths. Potential predictive efficacy and safety biomarkers are currently being assessed. Conclusions: The overall 3-year DFS rate does not reach the anticipated level for the main objective of the study. The multivariable analysis will determine if any subgroup of patients may benefit from this treatment scheme. Financed by Amgen S.A. Clinical trial information: NCT01285778.