In a Japanese phase III trial (JCOG1007; iPACS) reported in the Journal of Clinical Oncology, Kanemitsu et al found that the addition of primary tumor resection to chemotherapy did not improve overall survival vs chemotherapy alone in patients with asymptomatic primary colorectal cancer tumors and synchronous unresectable metastases.
The open-label multicenter trial included 165 patients with unresectable stage IV asymptomatic colorectal cancer and three or fewer unresectable metastatic sites confined to the liver, lungs, distant lymph nodes, or peritoneum. Patients were randomly assigned between June 2012 and September 2019 to receive primary tumor resection plus chemotherapy (n = 81) or chemotherapy alone (n = 84).
Chemotherapy consisted of either modified (m) FOLFOX6 (leucovorin, fluorouracil, oxaliplatin) plus bevacizumab or CAPOX (capecitabine, oxaliplatin) plus bevacizumab, with the choice decided prior to study entry. Among 67 patients in the primary tumor resection plus chemotherapy group and 79 in the chemotherapy group who started chemotherapy, 58 and 66 received the mFOLFOX6 regimen.
The primary endpoint was overall survival in the intention-to-treat population.
At first interim analysis, performed in September 2019 after 50% of expected events had been observed as of data cutoff (June 2019), the Data and Safety Monitoring Committee recommended early termination of the trial due to futility.
With a median follow-up of 22.0 months, median overall survival was 25.9 months (95% confidence interval [CI] = 19.9–31.5 months) in the primary tumor resection plus chemotherapy group vs 26.7 months (95% CI = 21.9–32.5 months) in the chemotherapy group (hazard ratio [HR] = 1.10, 95% CI = 0.76–1.59, P = .69). Median progression-free survival was 10.4 months vs 12.1 months (HR = 1.12, 95% CI = 0.81–1.55, P = .48).
In an updated analysis based on data through November 2019, overall survival at 3 years was 32.9% vs 33.0%. Median overall survival was 25.9 months vs 26.4 months (HR = 1.11, 95% CI = 0.78–1.58, P =.72)
Grade ≥ 2 surgery-related adverse events occurred in 29 (38%) of 77 patients who underwent primary tumor resection. Postoperative death occurred in three patients; death was considered treatment-related in two, with causes consisting of multiple organ failure and thromboembolism.
With regard to chemotherapy-related toxicity among patients starting chemotherapy, the frequency of grade ≥ 2 (87% vs 77%) and grade ≥ 3 adverse events (48% vs 34%) was higher in the primary tumor resection plus chemotherapy group.
The investigators concluded, “Given that primary tumor resection followed by chemotherapy showed no survival benefit over chemotherapy alone, primary tumor resection should no longer be considered a standard of care for patients with colorectal cancer with asymptomatic primary tumors and synchronous unresectable metastases.”
Yukihide Kanemitsu, MD, of the National Cancer Center Hospital, Tokyo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Center Research and Development Funds and an Applied Research for Innovative Treatment of Cancer grant from the Ministry of Health of Japan. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.