Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial
Background and Purpose
The role of primary tumor resection before chemotherapy in patients with advanced colorectal cancer who are asymptomatic and have synchronous unresectable metastases remains a contentious issue.
Patients and Methods
A randomized phase 3 clinical trial was initiated to determine the superiority of primary tumor resection followed by chemotherapy versus chemotherapy alone in relation to overall survival in patients with unresectable stage IV asymptomatic colorectal cancer and 3 or fewer unresectable metastatic disease confined to the liver, lungs, distant lymph nodes or peritoneum. Chemotherapy options included FOLFOX 6+ bevacizumab or capecitabine plus oxaliplatin plus bevacizumab. The primary endpoint was overall survival.
Between June 2012 and September 2018, 165 patients were randomly assigned to either arm, 84 for primary tumor resection versus 81 for chemotherapy alone. The first interim analysis was performed in September 2019. At that point 50% of the expected events observed among 260 patients at the data cut off in June 2019, and the authors concluded that there was futility hence the trial was terminated early. At a median follow-up of 22 months, median overall survival was 25.9 months in the primary tumor resection plus chemo arm versus 26.7 months, in the chemotherapy alone arm, hazard ratio 1.10, CI 0.76–1.59, one-sided P equals 0.69. There were 3 prospective deaths that occurred in the surgical arm.
The authors concluded that primary tumor resection followed by chemotherapy showed no survival benefit over chemotherapy alone. Primary tumor resection should no longer be considered standard of care for patients with colorectal cancer with asymptomatic primary tumors and synchronous unresectable metastases.