KEY TAKEAWAYS
- The FOLFIRINOX 3 phase I/II trial aimed to test the safety and effectiveness of a new chemotherapy regimen called bFOLFIRINOX-3 in mCRC pts.
- The primary endpoint was to measure the 2 months PFS. Secondary endpoints were ORR, median PFS, OS, and toxicity.
- The result showed better efficacy and safety than the standard care in treating chemorefractory mCRC.
Existing targeted therapies for chemorefractory mCRC have shown limited efficacy. Researchers aimed to test the safety and effectiveness of a new chemotherapy regimen called bFOLFIRINOX-3 in metastatic colorectal cancer (mCRC) patients(pts). In Phase I, bFOLFIRINOX-3 was defined with irinotecan at a specific 70mg/m² on day 1 and day 3.
The study included pts aged >18 years with an ECOG performance status of 0 or 1, pathologically confirmed mCRC, and previous treatment failure with standard chemotherapies (including at least 5-fluorouracil, oxaliplatin, and irinotecan). They required no residual neuropathy or history of grade 3 irinotecan-related toxicity. The treatment regimen comprised bevacizumab (5mg/kg), folinic acid (400mg/m²), 5-fluorouracil (2400mg/m² for 46 hours), oxaliplatin (85mg/m²), and irinotecan (70mg/m² administered before and after infusional 5-fluorouracil). CT scans were conducted every 2 months. The primary endpoint was 2-month progression-free survival (PFS), while secondary endpoints included the objective response rate (ORR), median PFS, overall survival (OS), and toxicity evaluation.
About 25 pts(age range: 50-70 years) were enrolled, with a median age of 62. They had received a median of 3 prior chemotherapy lines(range: [1-6]). The median follow-up period was 11 months (range:3-31.3 months). The 2-month PFS rate was 100%. The overall response rate was 17.4%. Median PFS was 7.8 months (IC95%[5.9;9.5]), and median OS was 31.3 months (IC95% [12.4; NR]). Grade 3 adverse events(AEs) occurred in [43.5%] with mostly diarrhea (39.1%) and neutropenia (21.7%). Grade 3 diarrhea was consistently resolving after a dose reduction of chemotherapy. The most common drug-related AEs (all grades) were fatigue (60.9%), diarrhea (73.9%), nausea (39.1%), peripheral neuropathy (47.8%), thrombocytopenia (82.6%), and anemia (56.5%).
The result showed better efficacy and safety than the standard of care in treating chemorefractory mCRC. The study met its primary endpoint and supported a randomized phase III trial.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e15563
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03795311
Jean-David Fumet, Aurelie Bertaut, Nicolas Roussot, Hélène Bellio, Leila Bengrine-Lefevre, Julie Vincent, Julie Niogret, Rémi Palmier, Thomas Collot, Laurie Rambach, Axelle Boudrant, Sophie Parnalland, Emilie Rederstorff, Audrey Hennequin, Sylvie Zanetta, Alice Hervieu, and François Ghiringhelli. DOI: 10.1200/JCO.2023.41.16_suppl.e15563 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) e15563-e15563.
