Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer

The ALASCCA phase III trial randomized patients with resected stage I-III rectal or stage II-III colon cancer and PI3K pathway alterations to adjuvant aspirin (160 mg daily) or placebo for 3 years. In those with PIK3CA mutations, aspirin significantly reduced 3-year recurrence (~7.5% vs ~15%) and improved 3-year DFS (~90% vs 80%). Severe AEs were higher with aspirin (16.8% vs 11.6%), but the number needed to treat (NNT) to prevent one recurrence was as low as 6 in stage III rectal cancer. For our colorectal cancer (CRC) patients with PI3K pathway mutations, adjuvant aspirin looks like a practical, low-cost targeted option worth considering in routine care. This may make more sense than celecoxib as the long-term risk of aspirin use is more defined, and the cardiovascular benefits may also be applicable to some patients.

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.

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.