{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:16:40Z","timestamp":1793686600354,"version":"4.5.1"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"\n Importance<\/jats:title>\n \n In patients with colorectal cancer and unresectable liver-only metastases (CRLM), treatment with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) plus irinotecan (FOLFOXIRI) and bevacizumab vs FOLFOX\/folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus bevacizumab increased progression-free survival, response, and R0\/R1 resection\/ablation rates, as well as toxic effects in\n RAS<\/jats:italic>\n \/\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n -variant and\/or right-sided tumors. FOLFOX\/FOLFIRI\u2013panitumumab vs FOLFOX\/FOLFIRI\u2013bevacizumab increased response at the cost of more toxic effects in\n RAS<\/jats:italic>\n \/\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n wild-type, left-sided tumors.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To present long-term outcomes of treatment with FOLFOXIRI plus bevacizumab vs FOLFOX\/FOLFIRI plus bevacizumab and FOLFOX\/FOLFIRI plus panitumumab vs FOLFOX\/FOLFIRI + bevacizumab.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n The randomized phase 3 CAIRO5 trial included patients with initially unresectable CRLM in 46 Dutch centers and 1 Belgian center between November 2014 and January 2022. A liver expert panel repeatedly evaluated resectability.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n \n Patients with\n RAS<\/jats:italic>\n \/\n BRAF<\/jats:italic>\n V600E<\/jats:sup>\n -variant and\/or right-sided tumors randomly received FOLFOX\/FOLFIRI\u2013bevacizumab (group 1) or FOLFOXIRI-bevacizumab (group 2), and those with\n RAS<\/jats:italic>\n \/\n BRAF<\/jats:italic>\n V600E<\/jats:sup>\n wild-type, left-sided tumors received FOLFOX\/FOLFIRI\u2013bevacizumab (group 3) or FOLFOX\/FOLFIRI\u2013panitumumab (group 4). Adjuvant chemotherapy (ACT) after complete local treatment was recommended but not standard.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Overall survival (OS) was analyzed as a secondary outcome. Other outcomes were post hoc analyses.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 530 patients (327 male [62%] and 203 female individuals [38%]; median age, 62 [IQR, 54\u201369] years) were randomized: 148 in group 1, 146 in group 2, 118 in group 3, and 118 in group 4. The median OS in group 1 was 23.6 (95% CI, 20.1-27.5) vs 24.1 (95% CI, 21.0-30.9) months in group 2 (hazard ratio [HR], 0.90; 95% CI, 0.70-1.17;\n P<\/jats:italic>\n \u2009=\u2009.44), and 39.9 (95% CI, 30.7-44.6) in group 3 vs 38.3 (95% CI, 35.3-51.3) months in group 4 (HR, 0.95; 95% CI, 0.68-1.32;\n P<\/jats:italic>\n \u2009=\u2009.75). OS was longest after complete local treatment without early (\u22646 months) recurrence (64.3 months; 95% CI, 57.6 to not reached) and salvage local treatment options after early recurrence (58.9; 95% CI, 47.3 to not reached), followed by patients without salvage local treatment after early recurrence (30.5; 95% CI, 24.4-33.4) and with incomplete local treatment (28.7; 95% CI, 25.9-38.3), and worst in patients with continued unresectability (18.3; 95% CI, 15.7-20.0). After confounder adjustment, ACT was associated with longer OS (HR, 0.66; 95% CI, 0.44-0.98) and relapse-free survival (HR, 0.65; 95% CI, 0.48-0.88) and less early recurrence without salvage local treatment (odds ratio, 0.46; 95% CI, 0.25-0.85).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n These results support using FOLFOX\/FOLFIRI\u2013bevacizumab for patients with initially unresectable CRLM irrespective of\n RAS<\/jats:italic>\n \/\n \n BRAF\n V600E<\/jats:sup>\n <\/jats:italic>\n status and tumor sidedness. Patients with complete local liver treatment with salvage local treatment in case of early recurrence had the longest OS. ACT might be considered for these patients.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov\n NCT02162563<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.5174","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T11:00:39Z","timestamp":1732186839000},"page":"36","source":"Crossref","is-referenced-by-count":39,"title":["First-Line Systemic Treatment for Initially Unresectable Colorectal Liver Metastases"],"prefix":"10.1001","volume":"11","author":[{"given":"Marinde J. 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