TRIBE studies underline survival benefit of FOLFOXIRI-bevacizumab in mCRC
Augmenting the triple chemotherapeutic regimen FOLFOXIRI* with bevacizumab demonstrated favourable efficacy regardless of age and gender in patients with unresectable metastatic colorectal cancer (mCRC), according to data presented at the ESMO World Congress on Gastrointestinal Cancer (ESMO GI) 2019.
To establish the safety and efficacy of upfront chemotherapy intensification according to baseline age and gender, researchers conducted a pooled subgroup analysis of the TRIBE** and TRIBE2*** studies (n=1,187, 58 percent male). Age-wise, 85 percent and 15 percent of participants were aged <70 and 70–75 years, respectively. Participants were randomized to receive bevacizumab in addition to either FOLFOXIRI (triplet-bevacizumab regimen) or a doublet regimen (ie, FOLFIRI# or FOLFOX##). [ESMO GI 2019, abstract O-013]
Objective response rate (ORR) and progression-free survival (PFS) benefit were improved with the triplet-bevacizumab regimen independent of age (pinteraction>0.05 for both ORR and PFS) and gender (pinteraction>0.05 for both).
However, regardless of treatment regimen, grade 3/4 AEs rates were generally higher in the older vs younger cohort (70 percent vs 57 percent; p<0.01) and among females vs males (65 percent vs 55 percent; p<0.01).
In the safety population, the triplet-bevacizumab regimen yielded a higher risk of overall and chemotherapy-related grade 3/4 adverse events (AEs) than the doublet-bevacizumab regimen regardless of age (pinteraction=0.74 and 0.79 for overall and chemotherapy-related AEs, respectively) and gender (pinteraction=0.63 and 0.33, respectively).
When comparing older vs younger participants, the triplet-bevacizumab regimen generated higher rates of grade 3/4 diarrhoea (27 percent vs 17 percent; p=0.02) and febrile neutropenia (16 percent vs 6 percent; p<0.01), while when comparing female vs male participants, higher rates of any-grade vomiting (50 percent vs 34 percent; p<0.01) and nausea (68 percent vs 59 percent; p=0.03) were observed.
“[Given] the increased incidence of febrile neutropenia and diarrhoea with FOLFOXIRI/bevacizumab, the use of [granulocyte-colony stimulating factor] as primary prophylaxis or an initial dose reduction of irinotecan and 5-fluorouracil might be considered in this population,” said the researchers. The high incidence of nausea and vomiting may warrant amplification of antiemetic prophylaxis, they added.
The survival advantage of the triplet-bevacizumab regimen over doublet-bevacizumab was also observed in a separate analysis of TRIBE2 as reflected by the significant improvement in PFS1 (12.0 vs 9.8 months, hazard ratio [HR], 0.75, 95 percent confidence interval [CI], 0.63–0.88; p<0.001), PFS2 (19.1 vs 17.5 months, HR, 0.74, 95 percent CI, 0.62–0.88; p<0.001), and overall survival (27.6 vs 22.6 months, HR, 0.81, 95 percent CI, 0.67–0.98; p=0.033). [ESMO GI 2019, abstract LBA-007]
The treatment effect with the triplet-bevacizumab regimen was consistent across clinical and molecular subgroups, with higher PFS2 benefit among individuals with ECOG performance status (PS) 0 vs those with ECOG PS 1–2 (HR, 0.70 vs 1.13; pinteraction=0.05).
The survival advantage of triplet-bevacizumab over the doublet-bevacizumab regimen was also observed in the presence of a right-sided and/or RAS/BRAF mutant tumour (HRs, 0.69 and 0.68 for PFS1 and PFS2, respectively), though these findings were nonsignificant.
Taken together, despite the relative increase in toxicity in the pooled analysis, both studies highlighted the efficacy of the triplet regimen when bevacizumab was added as an upfront option in treating unresectable mCRC.