• TRIBE
• TRIBE2

FOLFOXIRI + Bevacizumab is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer patients (mCRC). However, some concerns remain about subsequent second-line therapy, as failure of an oxaliplatin and irinotecan-based regimen may limit the clinical benefit of their reintroduction. In order to explore the feasibility of therapies following upfront FOLFOXIRI + Bevacizumab, we retrospectively analyzed the efficacy of second-line treatments after first-line triplet + Bevacizumab failure in patients recruited in the phase III TRIBE (NCT00719797) and TRIBE2 (NCT02339116) studies. Furthermore, we investigated the correlation between the efficacy of FOLFOXIRI reintroduction and oxalilplatin and irinotecan free interval (OIFI), determined as the time from the last administration of these two agents to disease progression.Among the 1187 screened patients, 588 were treated with upfront FOLFOXIRI + Bevacizumab. 419 patients received a second-line therapy and were included in the analysis. Efficacy and activity were explored as Progression Free Survival to second-line therapy (2nd PFS), Overall Survival (OS) and Overall Response Rate (ORR). The OIFI cut-off value was set to 4 months.
A second-line treatment was administered in 419 (80%) out of 527 patients progressed to upfront FOLFOXIRI + Bevacizumab. 176 (42%) were retreated with FOLFOXIRI ± Bevacizumab, gaining an advantage in ORR (22.7% vs 13.7%, p=0.011) and 2nd PFS over other regimens (6.1 vs 4.2 months, p=0.004). In the subgroup retreated after an OIFI > 4 months, triplet chemotherapy (CT) ± Bevacizumab outperformed doublet CT ± Bevacizumab (7.2 vs 5.5 months, p=0.017). FOLFOXIRI ± Bevacizumab reintroduction was not superior to other second-line treatments in terms of OS (13.7 vs 11.9 months, p=0.49). Progression to first-line FOLFOXIRI + Bevacizumab does not preclude the administration of an intensive and active second-line CT. Patients readministered with oxalilplatin and irinotecan after a longer OIFI seem to derive a greater advantage respect to the use of other strategies.