PMID- 38138211 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20240102 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 59 IP - 12 DP - 2023 Dec 1 TI - Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in BRAF(V600E)-Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study. LID - 10.3390/medicina59122108 [doi] LID - 2108 AB - Background and Objectives: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAF(V600E) mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAF(V600E)-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAF(V600E)-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAF(V600E)-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups. FAU - Tsai, Hsiang-Lin AU - Tsai HL AUID- ORCID: 0000-0002-1645-2525 AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Huang, Ching-Wen AU - Huang CW AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chen, Yen-Cheng AU - Chen YC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Su, Wei-Chih AU - Su WC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chang, Tsung-Kun AU - Chang TK AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chen, Po-Jung AU - Chen PJ AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Li, Ching-Chun AU - Li CC AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Chang, Yu-Tang AU - Chang YT AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Division of Pediatric Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. FAU - Wang, Jaw-Yuan AU - Wang JY AUID- ORCID: 0000-0002-7705-2621 AD - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. AD - Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. LA - eng PT - Journal Article PT - Observational Study DEP - 20231201 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 2S9ZZM9Q9V (Bevacizumab) RN - 7673326042 (Irinotecan) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) RN - XT3Z54Z28A (Camptothecin) RN - U3P01618RT (Fluorouracil) RN - EC 2.7.11.1 (BRAF protein, human) SB - IM MH - Humans MH - Bevacizumab/adverse effects MH - Irinotecan/therapeutic use MH - Proto-Oncogene Proteins B-raf/genetics MH - *Colorectal Neoplasms/drug therapy/genetics/pathology MH - Retrospective Studies MH - Preliminary Data MH - Camptothecin/adverse effects MH - Fluorouracil/therapeutic use MH - *Colonic Neoplasms/drug therapy MH - *Rectal Neoplasms MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects PMC - PMC10745094 OTO - NOTNLM OT - BRAFV600E mutation OT - UGT1A1 polymorphism OT - irinotecan dose escalation OT - metastatic colorectal cancer OT - overall survival OT - progression-free survival COIS- The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this article. EDAT- 2023/12/23 12:43 MHDA- 2023/12/25 06:42 PMCR- 2023/12/01 CRDT- 2023/12/23 01:14 PHST- 2023/09/16 00:00 [received] PHST- 2023/11/17 00:00 [revised] PHST- 2023/11/21 00:00 [accepted] PHST- 2023/12/25 06:42 [medline] PHST- 2023/12/23 12:43 [pubmed] PHST- 2023/12/23 01:14 [entrez] PHST- 2023/12/01 00:00 [pmc-release] AID - medicina59122108 [pii] AID - medicina-59-02108 [pii] AID - 10.3390/medicina59122108 [doi] PST - epublish SO - Medicina (Kaunas). 2023 Dec 1;59(12):2108. doi: 10.3390/medicina59122108.