P-061 Real-world experiences of use of aflibercept in patients with stage IV colorectal cancer in the North-West of England

Abstract

Introduction: Colorectal cancer is the third most common cancer worldwide, accounting for 13% of new cancer cases annually. The prognosis for metastatic colorectal cancer is poor, with a median overall survival of 18‐24 months. Systemic treatment options include cytotoxic agents (5‐FU in combination with irinotecan or oxaliplatin) and biological targeted agents. The development and introduction of anti‐angiogenic agents such as aflibercept has been shown to improve progression‐free survival and overall survival in patients with metastatic colorectal cancer. Methods: A list was obtained of patients who were prescribed aflibercept for stage IV bowel cancer in the Christie NHS Foundation Trust and Lancashire & South Cumbria Networks between January 2013 and January 2015. Data was then collected from electronic notes and online prescription systems regarding patient demographics, details of diagnosis, treatment, and toxicity. The results were then analysed using Microsoft Excel 2010. Results: Ninety‐five patients received aflibercept within the Christie NHS Foundation Trust (n = 60) and Lancashire & South Cumbria Cancer Network (n = 35). All patients had received prior combination 5FU‐oxaliplatin based chemotherapy, and received aflibercept with 5FU/irinotecan‐combination chemotherapy. 31.6% had previously received bevacizumab. The number of cycles given ranged from 0 to 48 (mean = 7.0, median = 5.0) including one patient still on treatment. In 87 patients in whom radiological response was assessed, best response to treatment was complete response (CR) in 1.1%, partial response (PR) in 31.0%, stable disease in 28.7% and progressive disease in 40.2%. 31% of patients with a KRAS mutation and 38.7% with KRAS wild‐type were responders (CR or PR). Reasons aflibercept was stopped included toxicity (42.1%), disease progression (26.3%), surgery (6.3%), clinical deterioration (5.3%), treatment completion (5.3%), patient death (3.2%), patient preference (2.1%), moving away (1.1%) and was unknown in 7.4%. Toxicities were reported in 88 patients (92.6%). Most common was fatigue (66.3%; 8.4% grade 3‐4) and diarrhoea (61.1%; 6.3% grade 3). 12.6% developed neutropaenia, (6.3% grade 3‐4), 18.9% developed hypertension (9.5% grade 3‐4) and 5.3% reported proteinuria (3.2% grade 3‐4). Following treatment completion/cessation, 45 (47.3%) patients received further treatment such as chemotherapy and/or targeted agents, surgery or radiotherapy. Twenty eight patients (29.5%) received palliative care. Conclusion: The objective response rate (ORR) to aflibercept in VELOUR, a multi‐centre, randomised, placebo‐controlled phase III trial comparing aflibercept with placebo in combination with FOLFIRI in 1226 patients, was 19.8%. In our audit the ORR was 31.8%. This disparity between the VELOUR study and our data could be due to the smaller size of our patient population and/or the differences in patient selection and radiological assessments. Common adverse events including diarrhoea and fatigue occurred at a similar incidence to those in VELOUR. However the incidence of proteinuria and hypertension were lower likely due to underreporting and recording of these out of a clinical trial setting. Aflibercept was removed from the list of Cancer Drugs Fund approved drugs list January 2015. However, numerous studies into the use of aflibercept in colorectal patients are ongoing. Overall our data showed a good response rate to aflibercept, it was well tolerated, and half of patients went on to further treatment.