PMID- 33347731 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20231213 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 10 IP - 2 DP - 2021 Jan TI - Early hypertension and neutropenia are predictors of treatment efficacy in metastatic colorectal cancer patients administered FOLFIRI and vascular endothelial growth factor inhibitors as second-line chemotherapy. PG - 615-625 LID - 10.1002/cam4.3638 [doi] AB - BACKGROUND: Three vascular endothelial growth factor (VEGF) inhibitors, Bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are widely used for metastatic colorectal cancer (mCRC) patients who are treated with second-line chemotherapy. The difference in outcome between the three drugs has not been evaluated. In contrast to epidermal growth factor receptor inhibitors, VEGF inhibitors have few candidate predictors of efficacy. METHODS: Consecutive mCRC patients who were treated with second-line chemotherapy were retrospectively enrolled. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were assessed. Subgroup analyses of prognostic and predictive efficacy markers were performed. RESULTS: A total of 119 (41.2%), 107 (37.0%), and 63 patients (21.8%) were treated with FOLFIRI +BEV, RAM, or AFL, respectively. ORR, PFS, and OS showed no significant differences between three groups. However, the frequency of grade 3 or 4 adverse events (AEs) in the FOLFIRI +AFL group was significantly higher than that in the other groups (p < 0.001). Patients with grade 3 or 4 AEs, especially hypertension and neutropenia within the first four cycles of treatment had significantly longer PFS and OS than those without AEs, irrespective of treatment with VEGF inhibitors (p < 0.001). PFS in patients without prior BEV exposure was also significantly longer than that in patients with prior BEV exposure (p = 0.003). CONCLUSIONS: Chemotherapeutic efficacy did not differ between the groups. Grade 3 or 4 AEs within the first four cycles of treatment and prior BEV exposure may be an effective predictor of treatment efficacy in mCRC patients administered VEGF inhibitors as second-line chemotherapy. CI - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Osumi, Hiroki AU - Osumi H AUID- ORCID: 0000-0002-4742-0446 AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Shinozaki, Eiji AU - Shinozaki E AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Ooki, Akira AU - Ooki A AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Wakatsuki, Takeru AU - Wakatsuki T AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Kamiimabeppu, Daisaku AU - Kamiimabeppu D AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Sato, Taro AU - Sato T AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Nakayama, Izuma AU - Nakayama I AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Ogura, Mariko AU - Ogura M AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Takahari, Daisuke AU - Takahari D AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Chin, Keisho AU - Chin K AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. FAU - Yamaguchi, Kensei AU - Yamaguchi K AD - Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20201221 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Recombinant Fusion Proteins) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 15C2VL427D (aflibercept) RN - 2S9ZZM9Q9V (Bevacizumab) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) RN - Q573I9DVLP (Leucovorin) RN - U3P01618RT (Fluorouracil) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Bevacizumab/administration & dosage MH - Camptothecin/administration & dosage MH - Colorectal Neoplasms/*drug therapy/pathology MH - Female MH - Fluorouracil/administration & dosage MH - Follow-Up Studies MH - Humans MH - Hypertension/chemically induced/*diagnosis/epidemiology MH - Japan/epidemiology MH - Leucovorin/administration & dosage MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Neutropenia/chemically induced/*diagnosis/epidemiology MH - Prognosis MH - Receptors, Vascular Endothelial Growth Factor/administration & dosage MH - Recombinant Fusion Proteins/administration & dosage MH - Retrospective Studies MH - Survival Rate MH - Vascular Endothelial Growth Factor A/*antagonists & inhibitors MH - Ramucirumab PMC - PMC7877370 OTO - NOTNLM OT - angiogenesis inhibitors OT - colorectal cancer OT - drug response biomarkers OT - vascular endothelial growth factors COIS- The authors declare that they have no conflict of interest. EDAT- 2020/12/22 06:00 MHDA- 2021/07/20 06:00 PMCR- 2020/12/21 CRDT- 2020/12/21 17:14 PHST- 2020/07/23 00:00 [received] PHST- 2020/11/11 00:00 [revised] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/12/22 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2020/12/21 17:14 [entrez] PHST- 2020/12/21 00:00 [pmc-release] AID - CAM43638 [pii] AID - 10.1002/cam4.3638 [doi] PST - ppublish SO - Cancer Med. 2021 Jan;10(2):615-625. doi: 10.1002/cam4.3638. Epub 2020 Dec 21.