Randomized clinical trial on resection of the primary tumor versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases.

Abstract

LBA3507 Background: Systemic chemotherapy improves survival of patients with stage IV colon cancer who are no candidates for curative therapy. However, it has remained controversial, if primary tumor resection prior to chemotherapy further prolongs survival of these patients. We report the combined results of the SYNCHRONOUS and CCRe-IV trial, comparing primary tumor resection followed by systemic chemotherapy to systemic chemotherapy alone in stage IV colon cancer patients. Methods: The SYNCHRONOUS trial (ISRCTN30964555) is a multicentre, randomized, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases were eligible for inclusion. Exclusion criteria were primary tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumor as well as systemic chemotherapy was provided according to the standards of the participating institution. The primary endpoint was overall survival (OS) with a minimum follow-up of 36 months (ITT population). An interim analysis yielded a pooled median survival time of 18 months. Assuming a difference of 6 months in median survival (15 vs. 21 months) with a two-sided type I error of 5%, power of 80% and an additional recruitment of 15% the total sample size amounted to n=392 patients (n=196 per arm). In order to accelerate reporting of the primary endpoint, data were pooled with the Spanish CCRe-IV trial (NCT02015923) with similar eligibility criteria, interventions and endpoints. Results: Between September 2011 and March 2013, 393 patients were randomized to primary tumor resection before chemotherapy (PTR; n=187) or chemotherapy alone (CTX; n=206) at 100 centers. The final study cohort included n=295 (75.1%) patients from the SYNCHRONOUS trial and n=98 (24.9%) patients from the CCRe-IV trial. The median follow-up was 36.7 months (95% CI: 36.6-37.3). Median OS was 16.7 months (95% CI: 13.2-19.2) in the PTR arm and 18.6 months (95% CI: 16.2-22.3) in the CTX arm. On final analysis, there was no significant difference for OS (HR 0.95, 95% CI: 0.743-1.215; p-value: 0.685), based on a proportional hazard model (shaired frailty). A total of 45 (24.1%) and 13 (6.4%) patients did not receive any chemotherapy in the PTR and CTX arm, respectively. In line with these data, the number of serious adverse events (excluding postoperative complications) was not different in the CTX arm (44; 20.7%) compared with the PTR arm (24; 12.5%). Conclusions: Resection of the primary tumor before chemotherapy does not prolong OS in patients with newly diagnozed, stage IV colon cancer and synchronous unresectable metastases. Clinical trial information: ISRCTN30964555.