PD-14 Resectability, conversion, and resection rates with survival according to RAS and BRAF mutations in a prospective metastatic colorectal cancer study (liver-limited subgroup in the RAXO study)

RAS and BRAF mutations are associated with worse outcomes for patients colorectal cancer (CRC) liver metastases, but little is known about their effects on resectability, conversion, resection rates. The prospective Finnish RAXO-study (NCT01531621) included 1086 treatable metastatic CRC 2012-2018 (Osterlund TLRHE 2021, Isoniemi BJS 2021) of which 354 RAS/BRAFV600E status liver-limited metastases at baseline were in this secondary endpoint analysis. Resectability was assessed repeatedly a tertiary centre multidisciplinary team meeting (MDT). Resectability, rates after R0/1-resection only studied according to mutational status. study 123 RAS&BRAF wild type (wt), 209 mutated (mt) 22 BRAFmt patients. Demographics RAS&BRAFwt/RASmt/BRAFmt, respectively, showed significant differences male proportion (72%/59%/46%) location primary (right colon 9%/30%/64%, left 62%/38%/23%, rectum 29%/32%/14%). RAS&BRAFwt, RASmt, had high upfront-resectability 48%, 45%, 27% conversion 25%, 22%, 18% (of all included), centralized MDT assessment. Corresponding 71%/60%/41% (OR reference/0.62 [CI95% 0.38-0.99]/0.29 [0.11-0.73]). When patient considered upfront resectable MDT, the local hospital underestimated resectability 39%/43%/83%, respectively. borderline resectable, assessment never 16%/15%/0%. Reasons not operating technically progressive disease during neoadjuvant therapy (63%), comorbidities (26%), inoperable exploratory surgery (11%). In 80% (31/39) 82% (45/55) 40% (4/10) BRAFmt. left-sided primaries (colon/rectum), (31/38) 87% (33/38) 100% (3/3) BRAFmt, right-sided they 0% (0/1) 71% (12/17) 14% (1/7) Conversion 90% (17/19) doublet chemotherapy + cetuximab/panitumumab, 89% (39/44) doublet/triplet bevacizumab, 69% (11/16) 1-2 drugs (1-2 cytotoxics +/- biologic). With cancers cetuximab/panitumumab-based, 55% (11/20) bevacizumab-based, 50% (2/4) drugs. From first 1-year recurrence-free survival 64%/58%/29% R0/1-resected RAS&BRAFwt/RASmt/BRAFmt (n=197), median overall (mOS) 82/73/28 months (HR reference/1.55 [0.91-2.65]/7.24 [2.38-22.00]), 5-year OS-rates 68%/60%/0%. diagnosis mOS R0/R1 resected 83/75/30 months, while R2-resection or ablation ‘not reached’/37/16, ‘systemic only’ 27/19/19, High rates, excellent achievable RAS&BRAFwt RASmt slightly inferior Highest (80-90%) seen primaries. Mutations sidedness should preclude proper repeated preferably organ-specific MDTs.