Maintenance CAP-B improves outcomes in mCRC across mutational subgroups
Maintenance treatment with capecitabine plus bevacizumab (CAP-B) following six cycles of capecitabine, oxaliplatin and bevacizumab (CAPOX-B) in metastatic colorectal cancer (mCRC) patients appears to provide a survival benefit across all mutational subgroups, according to a posthoc analysis of the CAIRO3 study. The effect of CAP-B on survival is most pronounced in patients with RAS/BRAF wild-type and V600EBRAF-mutant tumours.
The phase III CAIRO3 study included a total of 557 previously untreated mCRC patients (median age 64 years; 65 percent male) with stable disease or better after six cycles CAPOX-B induction treatment. These patients were randomly assigned to either the group receiving CAP-B maintenance treatment (n=278) or the group subjected to only observation (n=279). Upon first progression, CAPOX-B was reintroduced until second disease progression. [Lancet 2015;385:1843-52]
In the present analysis, the authors defined patient subgroups according to RAS/BRAF mutation and mismatch repair (MMR) status, and subsequently examined its impact on CAP-B treatment efficacy. It was found that 240/420 (58 percent) of patients had RAS mutation, 36/381 (9 percent) had BRAF, and 4/279 (1 percent) had MMR deficiency. [Ann Oncol 2017;doi:10.1093/annonc/mdx322]
At a median follow-up of 87 months (interquartile range, 69 to 97), all mutational subgroups demonstrated a significant improvement in the primary endpoint of second progression-free survival (PFS2), defined as the interval between randomization and second disease progression while under CAPOX-B reintroduction.
Prognosis was found to be more favourable for patients with V600EBRAF-mutant (hazard ratio [HR], 0.28; 95 percent CI, 0.12 to 0.64; p=0.002) or RAS/BRAF wild-type tumours (HR, 0.57; 0.39 to 0.84; p=0.004) than for patients with RAS-mutant tumours (HR, 0.74; 0.55 to 0.98; p=0.038).
Maintenance CAP-B also produced significant improvements in the other endpoints investigated (interval between randomisation until first progression and interval between randomization until second progression on any treatment), with the exception of overall survival (OS).
“[T]he RAS/BRAF wild-type and V600EBRAF mutant subgroups showed significant [OS] benefit from maintenance treatment in contrast to the RAS mutant subgroup [HR, 0.68; p=0.047 and HR, 0.32; p=0.007 vs HR, 0.98; p=0.867],” the authors noted.
Finally, when mutational subgroup analyses were adjusted for sidedness rather than primary tumour location, both right-sided and left-sided tumours were found to derive significant benefit from maintenance CAP-B.
Despite being limited by a potential bias related to the unavailability of the RAS/BRAF mutation status and MMR status for all patients, the “findings suggest that all mutational subgroups derive a significant benefit from maintenance treatment, which was most pronounced in patients with RAS/BRAF wild-type or V600EBRAF-mutant tumours,” the authors said.