Update of metastatic colorectal cancer metastases resection after FOLFIRI-aflibercept in oxaliplatin-refractory patients

Abstract

Introduction: Nowadays, the use of FOLFIRI-aflibercept (FA) is approved in metastatic colorectal cancer patients as second-line chemotherapy after tumoral progression with an oxaliplatin-based regimen. Recent data suggest that resection of metastatic colorectal cancer metastases after second-line chemotherapy offers similar overall survival benefit compared to what has been described in first-line. The improvement in response rate with FA as second-line therapy may increase the number of patients who eventually undergo metastases resection. Methods: We performed an observational, retrospective analysis of 39 patients from 32 Spanish hospitals who underwent metastases resection after FA in a real-life setting. The objective of this analysis is to analyze the efficacy and safety (surgical morbidity and mortality) or this regimen. Results: The median age was 62.5 years old (42-83). 74.4% of the patients were male and 25.6%, female. 61.5%presented ECOG 0 and 38.5%, ECOG 1. The primary tumors included were colon (71.8%) and rectum (28.2%). Tumor locations were: left 58.9%, right 30.8% and transverse 10.3%. RAS mutation was present in 71.8% of the tumors. The median follow up was 25.3 months (2.2-74.5). Most of the patients (68.4%) received a biological treatment combined with oxaliplatin-based chemotherapy: bevacizumab (n=16, 42.1%), cetuximab or panitimumab (n=9, 23.7%). All RAS wild-type tumors received anti-EGFR agents in first-line setting. Response rate to firstline chemotherapy: partial response (n=16, 42.1%), progressive disease (n=10, 26.3%), stabilization (n=8, 21.1%), and complete response (n=4, 10.5%). 37 patients (94.9%) received FOLFIRI-aflibercept as second line of treatment, with a median of 7 cycles prior to surgery (3-44). The best response to second line was partial response (n=22; 56.4%), followed by stabilization (n=15, 38.5%) and complete response (n=2, 5.1%). Types of surgery performed: liver metastases (n=18, 46.2%), pulmonary metastases (n=9, 23.1%), peritoneal carcinomatosis (n=6, 15.4%), others surgeries (n=2, 5.1%) and simultaneous liver and peritoneal carcinomatosis (n=4, 10.3%). Surgical results were the following: R0 (n=28, 73.7%), R1 (n=7, 18.4%) and R2 (n=3, 7.9%). 20.5% of patients presented with postsurgical complications: abdominal abcess (25%), anastomosis deshicence (10%), biliary fistula (12.5%) and infectious diseases (50%). No patient presented with bleeding complications. The 30- 90 days mortality rate was of 0%. 37.8% of the patients also received aflibercept postsurgery and a minor proportion (5.3%) required a second surgery. Median overall survival (mOS) after surgery (aSx) was 35.2 months (26.6-43.8). Median progression free survival (mPFS) aSx was 10 months (5.5-14.4). No difference in mOS between left and right side tumors was observed (P = .487). Conclusion: Resection of metastases after FA in oxaliplatin-refractory patients is safe and feasible with encouraging results in OS.