One or 2 doses pre op then completing a year of therapy lead to pCR in 53% of patients with MSI, the pCR increased from 46% after one dose to 68% after 2 doses.
Encouraging phase I signal for this HER2-targeted Antibody-drug conjugate (ADC) in heavily pretreated GI cancers, 45% overall response rate (ORR) and 16.3mo median overall survival (OS) in HER2-positive gastric compares favorably with T-DXd benchmarks, and the 40.5% objective response rate (ORR) with 22.7mo OS in HER2-positive colorectal cancer (CRC) is notable. The 2% ILD rate looks meaningfully better than T-DXd’s reported range, which could be a real differentiator. Hematologic toxicity is substantial but manageable. Small China-only phase I, but worth watching closely as this advances.
For high-risk patients with four or more colorectal liver metastases, adjuvant hepatic arterial infusion oxaliplatin roughly doubled hepatic recurrence-free survival versus standard IV chemotherapy (25 vs. 12 months), with recurrence-free survival (RFS) benefit as well. Overall survival (OS) didn't reach significance but the absolute difference and 5-year OS of 62% versus 47% suggest a real effect worth confirming in phase III. Toxicity was higher in the hepatic arterial infusion (HAI) arm but manageable with no treatment-related deaths. Generalizability remains the challenge, these needs specialized centers with HAI expertise, but worth keeping in mind for your highest-risk resected liver met patients.
The mature overall survival (OS) data from this Japanese randomized trial answer the question the initial publication left open, and the answer is no, adjuvant mFOLFOX6 after hepatectomy for resectable colorectal liver metastases does not improve overall survival (HR 1.07, P=.74), despite the previously reported DFS benefit. Five-year OS was numerically worse in the chemotherapy arm (73% vs 80%), though not significantly so. The disease-free survival (DFS) benefit was likely confounded by oxaliplatin-induced hepatic changes obscuring imaging and imbalances in post-recurrence therapy. Selection of patients and those with curable vs incurable intent surgery may have led to some bias in my opinion.
Open-label, phase 3 clinical trial, 382 patients were randomized to receive chemotherapy alone or chemotherapy plus tumor debulking. The overall survival rates were not statistically different, with a median overall survival in the chemotherapy alone group of 27.5 m vs 30.0 m in the chemotherapy plus tumor debulking group hence tumor debulking added to palliative systemic chemotherapy did not result in significantly improved survival compared with chemotherapy alone in patients with multiorgan metastatic colorectal cancer.
This is a strong adjuvant signal in resected stage III dMMR colon cancer, adding atezolizumab to mFOLFOX6 cut the risk of recurrence or death in half and improved 3-year DFS from 76% to 86%. OS hasn’t separated yet, but that may be confounded by immunotherapy at relapse. Toxicity was higher, as expected, with more grade 3–4 events and immune-related adverse events (AE)s, but overall manageable. This feels practice changing for stage III dMMR disease.
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.
People prefer stool card over colonoscopy, and it is not inferior.