Hepatectomy versus systemic therapy for liver-limited BRAF V600E-mutated colorectal liver metastases: multicentre retrospective study.

BACKGROUND: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings. METHODS: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort. RESULTS: Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88). CONCLUSION: BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs.

Upfront Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Bevacizumab With or Without Atezolizumab for Patients With Metastatic Colorectal Cancer: Updated and Overall Survival Results of the ATEZOTRIBE Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 4-year results of the phase II randomized AtezoTRIBE study. Eligible patients with metastatic colorectal cancer (mCRC) received first-line fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (control group, n = 73) or FOLFOXIRI/bevacizumab plus atezolizumab (experimental group, n = 145). We present overall survival (OS) and updated outcomes according to tumor immune-related biomarkers, both in the intention-to-treat (ITT) population and the cohort of patients with proficient mismatch repair (pMMR) tumors. Median follow-up was 45.2 months (IQR, 42.6-49.2). In the ITT population, median OS was 33.0 and 27.2 months for experimental and control groups, respectively (hazard ratio [HR], 0.78 [80% CI, 0.61 to 0.98]; P = .084). An interaction effect between Immunoscore Immune-Checkpoint (IC) and treatment arm was observed (Pint, .089), with higher benefit from atezolizumab in the Immunoscore IC-high group. In the pMMR cohort (N = 202), median OS was 30.8 and 29.2 months for experimental and control groups, respectively (HR, 0.80 [80% CI, 0.63 to 1.02]; P = .117). Interactions between treatment group and tumor mutational burden (TMB) and Immunoscore IC were reported (Pint, .043 and .092, respectively), with patients bearing TMB-high and Immunoscore IC-high tumors deriving higher benefit from the addition of atezolizumab. First-line FOLFOXIRI/bevacizumab plus atezolizumab improves OS in patients with mCRC. In the pMMR group, patients with Immunoscore IC-high and/or TMB-high tumors are identified as a subgroup of interest to further develop this treatment.