Use of Aflibercept (ZALTRAP) as Second Line Therapy in Patients with Metastatic Colorectal Cancer in Named Patient Program in India: Preliminary Analysis of Data from Six Centres

Abstract

Introduction: Aflibercept (Zaltrap) is a novel antiangiogenesis targeting agent, and in combination with FOLFIRI, it has been shown to improve outcomes in the VELOUR study (Van Cutsem et al, JCO 2012). After Aflibercept received priority approval in the USA (August 2012) to facilitate access to Indian patients who were prescribed the medicine, Sanofi made the drug available to Indian patients under a named patient access program. For safety reasons, it was made available only if the patient fulfilled the same criteria as the pivotal Velour study. We present the clinical experience with the use of Aflibercept in Indian patients. Methods: We have included data from patients that were administered aflibercept between October 2012 and January 2014, Aflibercept was given in combination with FOLFIRI for patients who failed first‐line oxaliplatin based therapy, at six Indian centres (21 patients from Tata Memorial Centre, Mumbai). Patients were screened for eligibility and informed of the unlicensed access to the drug. Institutional EC's of the respective hospitals were intimated of this program. Aflibercept was given at 4mg/kg IV fortnightly. Doses of chemotherapy were irinotecan 180mg/m2, leucovorin 400mg/m2, 5FU bolus 400mg /m2, 5FU continuous infusion 2400mg/m2 over 46 hours. Use of growth factors was allowed. Response evaluation was done after every 4 cycles as per institutional practice (not by RECIST as in the VELOUR study). Results: 30 patients consented and obtained approval to commence therapy. The median age was 41 years (range, 18‐80) and 50% were females. All patients were PS 0‐1, 21 patients had undergone surgery for the primary (rectum n = 7) and 8 (26%) patients had signet ring histology. 7 (23%) patients had baseline hypertension being treated with medications. Median number of cycles administered was 5 (range 2‐12). Common grade 3 and 4 toxicities were mucositis 8 (27%), diarrhea 7 (23%), neutropenia 3 (10%) and thrombocytopenia 4 (13%), hypertension 4 (13%), hyponatremia 2 (6%), and one patient each had perforation, VTE, bleeding and vomiting. Post 4 cycles (mid‐cycle response), response was assessed in 22 pts ‐ 6 (27%) had PR, 9 (41%) patients had SD and 7 (32%) had progressed on treatment. Final response was assessed in 19 patients ‐ no CR, 4 (21%) PR, 4 (21%) SD, and 11 (58%) PD. Conclusion: Compared to the VELOUR data, greater proportion of Indian patients had grade 3 and 4 mucositis, though the other toxicities were comparable. This may be related to poor nutrition and oral hygiene. Data for diarrhea and hypertension, was comparable. Indian patients had less neutropenia, which could possibly be due to omission of bolus 5FU from the FOLFIRI regimen. The response rates were comparable (final response rates VELOUR 19.8% and 21% in Indian pts).