An alternating regimen of modified CAPOX (mCAPOX) and modified CAPIRI (mCAPIRI) combined with bevacizumab has shown promising efficacy and acceptable safety in patients with previously untreated, unresectable metastatic colorectal cancer (mCRC), according to a recent phase 2 study. The findings suggest that this alternating chemotherapy schedule could be a valuable first-line treatment option for this patient population.
Efficacy and Outcomes
The study demonstrated that the alternating mCAPOX/mCAPIRI plus bevacizumab regimen resulted in a median progression-free survival (PFS) of 11.0 months (95% CI 9.0–12.4) and a median overall survival (OS) of 28.1 months (95% CI 18.4–34.0). The overall response rate (ORR) was 73% (95% CI 59–84%), with a depth of response (DpR) of 46.0% ± 26.3%.
These results compare favorably with previous studies of alternating doublet chemotherapy without bevacizumab, which reported median PFS/TTP ranging from 8.8 to 13 months and median OS ranging from 17.3 to 26.1 months. First-line triplet chemotherapy (FOLFOXIRI) without bevacizumab has shown median PFS/TTP of 8.4 to 10.8 months and median OS of 21.5 to 28.4 months.
Subgroup Analysis
Subgroup analyses indicated that the alternating chemotherapy schedule combined with bevacizumab provided better benefits in mCRC patients with a neutrophil-to-lymphocyte ratio (NLR) < 5 or RAS wild-type diseases. The regimen also demonstrated encouraging efficacy in mCRC patients with BRAF V600E mutation, achieving a median PFS of 11.6 months, which is better than triplet chemotherapy plus bevacizumab and doublet chemotherapy plus bevacizumab.
Safety Profile
The incidence rate of any grade treatment-related adverse events (TRAEs) was 96%, but only 33% of patients experienced grade 3 to 4 TRAEs. The most frequent grade 3 to 4 TRAEs included hypertension, decreased neutrophil count, and hand-foot syndrome, all of which were manageable. No patient died due to TRAEs, and no unexpected TRAEs were reported.
Notably, the alternating chemotherapy schedule regimen may have lower risks of decreased neutrophil count, peripheral neuropathy, and diarrhea compared to triplet and doublet chemotherapy. This is attributed to the lower dose intensity of oxaliplatin and irinotecan in the alternating regimen.
Cost-Effectiveness and Convenience
The alternating schedule of mCAPOX/mCAPIRI plus bevacizumab may be more cost-effective than triplet chemotherapy plus bevacizumab due to the lower doses of oxaliplatin and irinotecan. Additionally, the oral administration of capecitabine offers greater convenience and reduces expenses compared to fluorouracil, which requires a peripherally inserted central catheter or implanted port.
Study Limitations
The study acknowledges several limitations, including small sample sizes in subgroups and the lack of a head-to-head comparison with triplet chemotherapy combined with bevacizumab. The authors emphasize that the regimen of mCAPOX/mCAPIRI plus bevacizumab needs to be evaluated in randomized controlled trials in the future.
Clinical Implications
The study concludes that the alternating schedule of mCAPOX/mCAPIRI chemotherapy in combination with bevacizumab has promising efficacy in unresectable mCRC patients with no prior systemic treatment. The toxicities were acceptable and manageable, with no new safety signals identified. This regimen may represent a novel option for unresectable mCRC in the first-line setting, warranting further investigation in international randomized controlled trials.
