Abstract 43P
Background
In chemorefractory metastatic colorectal cancer (mCRC), TAS-102 plus bevacizumab or regorafenib showed a modest clinical benefit. A phase I of FOLFIRINOX3-bevacizumab (bFOLFIRINOX 3) defined the RP2D for irinotecan of 70mg/m2 and showed promising activity. The aim of this phase II trial was to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory mCRC.
Methods
Patients >18years and ECOG 0 or 1, with a pathologically confirmed mCRC were enrolled. Patients must have experienced treatment failure to chemotherapies that must include 5-fluorouracil, oxaliplatin and irinotecan. Absence of neuropathy and previous grade 3 irinotecan related toxicity was mandatory. Regimen consisted of bevacizumab (5mg/kg), folinic acid (400mg/m2), 5-fluorouracil (2400mg/m2 for 46h), oxaliplatin (85mg/m2) and irinotecan (70mg/m2 administered before and after infusional 5-fluorouracil). Primary endpoint was efficacy defined by 2-months PFS. Secondary endpoints included objective response (RECIST 1.1), median PFS, median overall survival (OS) and toxicity.
Results
32 patients were enrolled. Median age was 62.5 y (range: 32-78y). Patients have been treated with several previous lines of chemotherapy (median = 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). The 2-and 6-months PFS were 93.8% (IC95% [91-100]) and 71.9% (IC95% [57.9-89.3]) respectively. Overall response rate was 28.1% (IC95% [12.5-43.7]). Median PFS was 9.1 months (IC95% [6.9 ;11.5]) and median OS was not reached (IC95% [11.6; NR]). Grade 3 adverse events occurred in 81.2% with mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea was consistently resolving after a dose reduction of chemotherapy. The most common drug-related adverse events (all grades) were fatigue (78.1%), diarrhea (96.9%), nausea (68.7%), peripheral neuropathy (65.6%), thrombopenia (40.6%) and anemia (56.3%).
Conclusions
The combination of bFOLFIRINOX-3 yielded ORR of 28.1%, 6-months PFS of 71.9%. The regimen was well tolerated. These results are promising in a chemotherapy refractory mCRC and support for future randomized phase II compared to standard of care.
Clinical trial identification
NCT03795311.
Legal entity responsible for the study
The authors.
Funding
ARCAS ARCAD.
Disclosure
F. Ghiringhelli: Financial Interests, Institutional, Invited Speaker: BMS, MSD, Servier, Amgen, AstraZeneca; Financial Interests, Institutional, Advisory Board: Merck Serono; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen. All other authors have declared no conflicts of interest.