43O - Preoperative chemotherapy prior to primary tumor resection for colorectal cancer patients with asymptomatic resectable primary lesion and synchronous unresectable liver-limited metastases (RECUT): A prospective, randomized, controlled, multicenter clinical trial

Background

Primary tumor resection (PTR) was preferably performed for metastatic colorectal cancer (mCRC) with an asymptomatic resectable primary tumor and synchronous unresectable colorectal liver-limited metastases (CRLMs) with conversion therapy intent.

Methods

This randomized phase III study investigated the superiority of pre-PTR chemotherapy versus upfront PTR for these asymptomatic CRLMs patients. Chemotherapy regimens consisting of either mFOLFOX6 plus cetuximab, mFOLFOX6 plus bevacizumab or mFOLFOX6 alone were assessed according to the RAS genotype and patient affordability. The primary end point was progression-free survival (PFS), and secondary outcomes included overall survival (OS), tumor response, conversion rate to liver metastasis resection, surgical complications and chemotherapy toxicity.

Results

Between June 2012 and June 2018, 320 patients were randomly assigned to undergo pre-PTR chemotherapy (160 patients; arm A) or upfront PTR (160 patients; arm B). The median follow-up time was 36.2 months. Patients in arm A had significantly increased median PFS (10.5 v 9.1 months; hazard ratio = 0.755 [95% CI, 0.60 to 0.95]; P = 0.013) compared with arm B. Patients in arm A also had a significantly better disease control rate (84.4% v 75.0%; P = .037). The median OS (29.4 v 27.2 months; hazard ratio = 0.766 [95% CI, 0.58 to 1.01], P = .058), objective response rate (53.1% v 45.0%; P = .146) and actual resection rate of liver metastases (21.9% v 18.1%; P = .402) were not significantly different. Mild morbidities occurred and no 30-day postoperative mortalities in both arms, the Clavien–Dindo 3-4 complications post PTR did not reach statistical significance (4.5% v 3.8%, P = .759). The observed toxicity of chemotherapy was mostly mild, and there was no significant difference in the overall incidence of predefined grade 3/4 events (42.2% v 40.4%, P = .744).

Conclusions

Pre-PTR chemotherapy improves PFS in the treatment of these asymptomatic CRLMs patients over upfront PTR. Pre-PTR chemotherapy should remain the preferred reference treatment for these eligible patients.

Clinical trial identification

NCT01307878.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China (82072678); Clinical Research Plan of SHDC (No. SHDC2020CR1033B).

Disclosure

All authors have declared no conflicts of interest.