Impact of synchronous vs metachronous primary tumor resection on prognosis of BRAF-V600E mutant metastatic colorectal cancer (mCRC).

304 Background: The goal of this study is to evaluate if resection of the primary tumor in synchronous versus metachronous metastatic disease predicts survival of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR inhibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mutation mCRC who did not receive combination BRAF/anti-EGFR therapy, diagnosed with colorectal cancer prior to March 31, 2021. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included median duration of therapy and overall survival (OS). Results: 71 patients were included with a median age of 70 years:, 37 (52%) were females, 49 (69%)had right-sided tumors and 19 (27%) were mismatch repair deficient (dMMR). The primary tumor was unresected in 22 (30%) and resected in 49 (70%), completely resected in 44 (62%), and partially resected in 5 (7%) patients. Overall, median OS was 12.9 months 95% CI (8.4, 19) with 17 months 95% CI (11, —) mOS in patients with resected primary and 6.3 95% CI (4.8, 15) months in patients with unresected primary, HR 2.48 95% CI (1.42, 4.32), p=0.001. In univariate analysis: signet ring cell (p=0.007), good performance status (p<0.001), distant lymph nodes (p<0.001), peritoneal metastasis (p=0.008), metasetectomy (p=0.002), Charlston Comorbidity Index (p=0.003) were significant prognostic factors. Synchronous versus metachronous primary tumour was not a significant prognostic factor. Conclusions: Real world data confirms that patients with BRAF-V600E mutant mCRC have poor clinical outcomes. Our analysis suggests that resection of the primary tumor did not seem to impact on survival of BRAF-V600E mutant mCRC patients. This suggests that prognosis is dictated by the systemic disease and not complications of the primary tumour itself. Of the patients with unresected primary tumour (n=21), 6 were synchronous. Metastatic status Primary Tumor Resected Primary Tumor unresected Total Synchronous 23 22 45 Metachronous 26 0 26 Total 49 22 71