AbstractJCOG0603 demonstrated improved disease-free survival (DFS) with adjuvant mFOLFOX6 after hepatectomy compared with hepatectomy alone in colorectal liver-only metastasis (CRLM), but the overall survival (OS) data were immature. Here, we report OS after long-term follow-up. Eligible patients with colorectal adenocarcinoma and an unlimited number of liver metastases were randomized to adjuvant mFOLFOX6 or hepatectomy alone. DFS was the primary endpoint, and OS was a secondary endpoint. Between March 2007 and January 2019, 151 and 149 patients were randomized to adjuvant chemotherapy and hepatectomy alone, respectively. a median follow-up of 7.7 years for disease-free surviving patients, 54 (35.8%) and 51 (34.2%) patients had died in the respective arms, (hazard ratio [HR], 1.07 [95% CI, 0.73 to 1.57]). Five-year OS was 73.4% (95% CI, 65.5 to 79.7) and 80.1% (95% CI, 72.6 to 85.7) and 7-year OS was 69.4% (95% CI, 61.2 to 76.2) and 72.4% (95% CI, 64.2 to 79.1), respectively. One patient in the adjuvant chemotherapy arm possibly died of protocol treatment-related toxicity, and one in the hepatectomy-alone arm died of post-protocol treatment complications. Five-year DFS was respectively 49.7% (95% CI, 41.5 to 57.3) and 40.5% (95% CI, 32.5 to 48.3) in the adjuvant chemotherapy and hepatectomy-alone arms (HR, 0.72 [95% CI, 0.54 to 0.97]). Long-term OS did not differ with adjuvant mFOLFOX6 compared with hepatectomy alone in resectable CRLM. Adjuvant mFOLFOX6 may delay recurrence but did not improve long-term survival.
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.
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.