FOLFOXIRI Plus Bevacizumab Reinstated Post-Progression Preferable Strategy for mCRC

Upfront fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab reintroduced after progression is preferable to chemotherapy doublets in patients with metastatic colorectal cancer (CRC), according to results of the TRIBE2 phase 3 clinical trial (Lancet Oncol. 2020 Mar 9. Epub ahead of print).

“The triplet FOLFOXIRI…plus bevacizumab showed improved outcomes for patients with metastatic [CRC], compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression,” explained Chiara Cremolini, MD, Department of Oncology, University Hospital of Pisa, Italy, and colleagues.

Thus, Dr Cremolini et al sought to compare upfront FOLFOXIRI followed by reintroduction of the same regimen after disease progression versus mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets combined with bevacizumab.

A total of 679 patients with unresectable, previously untreated metastatic CRC were randomly assigned to receive treatment between February 2015 and May 2017.

This included 339 patients in the experimental arm given FOLFOXIRI plus bevacizumab followed by reintroduction of the same regimen after progression, and 340 patients in the control arm given mFOLFOX6 followed by FOLFIRI post-progression.

The primary end point was progression-free survival, and the median follow-up time frame was 35.9 months.

Overall, the experimental arm had a median progression-free survival of 19.2 months versus 16.4 months in the control arm.

Diarrhea, neutropenia, and arterial hypertension were the most frequent grade 3-4 adverse events (AEs) after first-line treatment, and serious AEs occurred in 25% of the experimental arm versus 17% of the control arm.

In total, 8 treatment-related deaths occurred in the experimental arm versus 4 in the control arm. No differences in grade 3 or 4 AEs were noted after disease progression between the experimental and control arms.

After disease progression, serious AEs occurred in 15% of patient in the experimental arm versus 12% of the control arm. Three additional treatment-related deaths after disease progression were reported in the experimental arm versus 4 in the control arm.

“Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic [CRC],” concluded Dr Cremolini and co-investigators.—Kaitlyn Manasterski