FOLFIRI plus bevacizumab (B) as neoadjuvant treatment for potentially resectable colorectal cancer patients (pts) with liver metastasis: A phase II trial.

Abstract

e14130 Background: Irinotecan-based chemotherapy plus B was shown to be effective and safe in both first- and second-line treatment for metastatic colorectal cancer (mCRC) pts.We designed this trial to assess whether the combination of FOLFIRI + B given to untreated, potentially resectable mCRC pts was feasible and active. Methods: Phase II, single arm trial with 1-year progression-free rate (PFR) as primary end-point. A sample size of 39 pts was calculated to detect a 70% ± 12% 1-year PFR. The treatment was FOLFIRI q2w (irinotecan 180 mg/m2, leucovorin 200 mg/m2, 5FU 2400 mg/m2 iv in 46 hrs) plus B 5mg/kg q2w. Last cycle before surgery was without B. Potentially resectable, untreated mCRC pts, with liver as unique site of metastases, were eligible. Normal organ function and no contraindications to B were required. Pts were reevaluated for surgery after 6 cycles. PET-Scan were performed at baseline and at the second cycle. Results: Overall 39 pts were enrolled. Median age was 58 (range 30-75), male/female were 24/15. Twenty seven pts (69.2%; 95%CI 52.4% – 83.0%) were progression-free at 1-year. Thirty seven pts (94.9%) underwent surgery. One complete and 22 partial responses were observed (response rate 59.0%; 95% CI 42.1% – 74.4%); 5 pts had disease progression (4 resectable and 1 unresectable). Early PET-scan was assessed according PERCIST criteria [Wahl RL, J Nucl Med 2009] in 29 pts and showed metabolic response (SUV-max decrease > 30%) in 17 (58.6%; 95% CI: 38.9%- 76.5%).Severe toxicity includes grade 3 neutropenia (3 pts, 7.7%) and grade 3 diarrhea (1 pt, 2.6%). Other toxicities include grade 1-2 diarrhea (15.4%), grade 2 nausea (7.8%), grade 2 leucopenia (5.1%), grade 2 asthenia (5.1%), grade 1 anemia (2.6%), grade 2 thrombosis (2.6%). Overall, 16 pts out of 37 experienced surgical complications (43.2%; 95%CI 27.1% - 60.5%): biliary leak (11 pts, 29.7%), biliary fistula (1 pt, 2.7%), other complications (4 pts, 10.8%). All complications were reversible. No peri-operative bleeding was observed. Conclusions: The trial yielded its primary aim and shows that FOLFIRI plus B is feasible and active as neo-adjuvant treatment in patients with resectable liver metastases of CRC.