AIMTo evaluate the efficacy and safety of the modified FOLFIRI3-aflibercept as second-line therapy in patients with metastatic colorectal cancer.METHODSThis is a retrospective multicenter cohort, evaluating the efficacy and safety of the association of aflibercept with FOLFIRI3 (day 1: aflibercept 4 mg/kg, folinic acid 400 mg/m2, irinotecan 90 mg/m2, 5-fluorouracil infusion 2400 mg/m2 per 46 h; day 3: irinotecan 90 mg/m2) in patients with previously treated metastatic colorectal cancer. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.RESULTSAmong 74 patients treated in four French centers, nine were excluded due to prior use of aflibercept (n = 3), more than one prior treatment line in irinotecan-naïve patients (n = 3), and inadequate liver function (n = 3). In the “irinotecan-naïve” patients (n = 30), ORR was 43.3% and DCR was 76.7%. Median PFS and OS were 11.3 mo (95%CI: 6.1-29.0) and 17.0 mo (95%CI: 13.0-17.3), respectively. The most common (> 5%) grade 3-4 adverse events were diarrhea (37.9%), neutropenia (14.3%), stomatitis and anemia (10.4%), and hypertension (6.7%). In the “pre-exposed irinotecan” patients (n = 35), 20 (57.1%) received ≥ 2 prior lines of treatment. ORR was 34.3% and DCR was 60.0%. Median PFS and OS were 5.7 mo (95%CI: 3.9-10.4) and 14.3 mo (95%CI: 12.8-19.5), respectively.CONCLUSIONMinimally modified FOLFIRI has improvement dramatically the FOLFIRI3-aflibercept efficacy, whatever prior use of irinotecan. A prospective randomized trial is warranted to compare FOLFIRI-aflibercept to FOLFIRI3-aflibercept.

817 Background: The efficacy of the standard FOLFIRI-aflibercept second-line therapy may be improved by the chemotherapy regimen in metastatic colorectal cancer (MCRC). FOLFIRI was optimized by splitting the dose of irinotecan on day 1 and day 3 and by removing the bolus of 5-FU in the FOLFIRI3 regimen. Methods: This is a retrospective multicentric cohort, evaluating efficacy and safety of the association of aflibercept with FOLFIRI3, in patients (pts) with previously treated MCRC. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: From September 2014 to December 2016, 74 pts were treated in four French centers. Nine pts were excluded due to prior use of aflibercept (n = 3), more than one prior line of treatment in irinotecan-naïve pts (n = 3) and inadequate liver function (n = 3). In the cohort of irinotecan-naïve pts (n = 30), ORR and DCR were 43.3% and 76.7%. Median PFS and OS were 11.3 months (95% CI 6.1-29.0) and 17.0 months (95% CI 13.0-17.3). The most common ( > 5%) grade 3-4 adverse events were diarrhea (37.9%), neutropenia (14.3%), stomatitis and anemia (10.4%), hypertension (6.7%). In the cohort of pts previously treated with irinotecan (n = 35), 20 (57.1%) pts received ≥2 prior lines of treatment with various prior irinotecan regimen (FOLFIRINOX, n = 21; FOLFIRI, n = 10; FOLFIRI3, n = 4). ORR and DCR were 34.3% and 60.0%. Median PFS and OS were 5.7 months (95% CI 3.9-10.4) and 14.3 months (95% CI 12.8-19.5). In 4 patients refractory to irinotecan, FOLFIRI3-aflibercept led to one partial response, 2 stabilizations, and one patient not evaluable. Conclusions: A minimal modification of the FOLFIRI regimen led to a dramatically improvement of efficacy with FOLFIRI3-aflibercept, whatever prior use of irinotecan. Further randomized trial is planned.