New first line standard of care for BRAF mutant colon cancer considering the possibility if chemotherapy is really needed. There may be future trials. This trial led to accelerated FDA approval of this regimen.
The BREAKWATER trial evaluated encorafenib, cetuximab, and mFOLFOX6 as a first-line therapy for BRAF V600E–mutated metastatic colorectal cancer, showing very significant improvements in progression-free survival (PFS) (12.8 vs 7.1mos) and overall survival (OS) (30.3 vs 15.1mos). The combo also achieved a higher overall response rate (ORR). (60 vs 40%), positioning it as a new standard for this challenging patient population. Of note, side effects like nausea, diarrhea, and neuropathy, which were more frequent with this regimen. I would use this in the appropriate patient.
People prefer stool card over colonoscopy, and it is not inferior.
Interesting study where intermittent FOLFIRI + pan was seemingly just as effective as continuous therapy. The ongoing Phase III IMPROVE-2 is the confirmatory trial and if positive could change standard practice. Of note, intermittent meant eight (8) cycles followed by a holiday until progression when it was reinitiated.
This PLK1-inhibitor seems extremely promising. This phase II trial studied pre-treated KRAS-mut patients with FOLFIRI + bev + study drug and the response rates and PFS were quite remarkable. Given the compelling results, they went from this study to a phase III 1L study.
Combination beat monotherapy is another option for MSI patients. Is combo better then pembro?
Here is a large phase-III well done study confirming what we knew from earlier studies, that ipilimumab plus nivolumab (Ipi+Nivo) is highly active and effective in the microsatellite instability-high metastatic colorectal cancer (MSI-high met-CRC) population. This is most likely more effective than single agent IO therapy but with higher rates of toxicity. When all things are equal, I would consider this to be the standard of care (SOC) in this context.
This Japanese study showed no benefit with the addition of oxaliplatin to fluoropyrimidine plus bevacizumab (5FU+bev) in patients who were aged 70-74 but unfit, or >=75. Interestingly survival was actually shorter in the patients who received oxaliplatin at 21.3 vs 19.7 months.
Overall survival (OS) improvement was not statistically significant in the study arm but is a non-chemotherapy option. Patients here had tumors with MSS.
Less maintenance is NOT NON-inferior, so it is inferior in patients with wild type BRAF metastatic colon cancer. So it is better to keep on the full regimen. Although, quality of life is better.