Efficacy and Safety of FOLFIRI/Aflibercept (FA) in Elderly Population with Mcrc after Failure of Oxaliplatin-Based Chemotherapy

Abstract Background Aflibercept (Af) significantly improves progression-free (PFS) and overall survival (OS) when added to FOLFIRI, in the overall population of patients (pts) pretreated with oxaliplatin-based therapy. A subset analysis of pts (>65years) included in the VELOUR trial, suggests a consistent benefit in OS in PFS, but increased grade 3-4 toxicity. Our hypothesis was that selected pts >70y with good PS could benefit from FA, provided they underwent a careful monitoring of toxicity. Methods Retrospective, multicenter, observational study of mCRC pts >70 years (y) treated with FA as part of routine clinical practice at 8 hospitals from the Galician Research Group on Digestive Tumours (GITuD). Results From 338 patients treated with FA between June 2013 to November 2018, 75 pts were recorded. Median age was 72.7 y (range 70-84 y), and 33.4% were >75y. 65.3% were male, 87.5% ECOG PS0-1, 42.5 % left-sided location, 76.0 % low grade, 59.5% RASmt and 77.3 % primary tumor resection. Prior therapy included bevacizumab (56%) and anti-EGFR agents (24%), only adjuvant treatment (5.3%). Median of FA cycles was 10 (range 1-35 cycles). Overall Response Rate (ORR) and disease control rate (DCR) were 30.7% and 65.4%, respectively. With a median follow-up of 27.1 months (m), median PFS was 6.6 m (95% CI, 5.3-7.9 m) and median OS was 15.1 m (95% CI, 12.5-17.8 m). The most common grade 3-4 toxicities overall were asthenia (21.3%), neutropenia (14.7%) and diarrhoea (14.7%). Af-related toxicities were hypertension (5.3%), dysphonia (5.3%) and proteinuria (2.7%). Two patients experienced grade 5 toxicity.This toxicity was managed with dose reduction of Af in 34.7% of cases, dose reduction of FOLFIRI on 56.0% and discontinuation of Af in 18.6%. Conclusions Older patients with mCRC are underrepresented in clinical trials. The VELOUR study included only 6.4% pts >75y of age and only 14% included in the substudy of patients >65y were >75y. Patients >65y treated with FA in the VELOUR trial experienced a high rate of G3-4 adverse events (89.3%). Our series confirms that with careful pt selection and dose adjustment based on toxicity, patients >70y can be treated with FA with a 52.0% of grade 3-4 toxicity, results that are comparable to those of younger patients. Legal entity responsible for the study Galician Research Group on Digestive Tumours (GITuD). Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.