PMID- 31676953
OWN - NLM
STAT- MEDLINE
DCOM- 20200722
LR  - 20231213
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 14
IP  - 6
DP  - 2019 Dec
TI  - Effect of Early Adverse Events on Survival Outcomes of Patients with Metastatic 
      Colorectal Cancer Treated with Ramucirumab.
PG  - 743-748
LID - 10.1007/s11523-019-00683-z [doi]
AB  - BACKGROUND: Studies of patients treated with bevacizumab and other vascular 
      epithelial growth factor (VEGF) inhibitors have reported that hypertension 
      adverse events (AEs) are associated with improved overall survival (OS) or 
      progression-free survival (PFS). OBJECTIVE: Our objective was to evaluate the 
      association between early AEs and survival outcomes for patients treated with 
      ramucirumab, an antibody targeting the VEGF receptor-2 (VEGFR-2), plus FOLFIRI 
      for metastatic colorectal cancer (mCRC). METHODS: Data from 529 patients treated 
      with ramucirumab plus FOLFIRI for mCRC in the RAISE clinical trial (NCT01183780) 
      were evaluated to see whether early (first 6 weeks of therapy) AEs predicted 
      subsequent OS and PFS. A Cox proportional hazard approach was used to evaluate 
      associations between early AEs and survival outcomes. A secondary analysis 
      between FOLFIRI and placebo was conducted as a sensitivity analysis. RESULTS: Of 
      529 patients treated with ramucirumab plus FOLFIRI, 479 were alive and 
      progression free at 6 weeks after commencing therapy. No significant association 
      was identified between hypertension occurring within the first 42 days of 
      ramucirumab plus FOLFIRI therapy and OS (grade 1-2, hazard ratio [HR] 0.90 [95% 
      confidence interval (CI) 0.66-1.24]; grade 3+, HR 1.02 [95% CI 0.67-1.55]; 
      P = 0.803) or PFS (grade 1-2, HR 0.98 [95% CI 0.74-1.28]; grade 3+, HR 0.93 [95% 
      CI 0.64-1.37]; P = 0.93). However, there was a significant association between 
      diarrhea occurring within the first 42 days of ramucirumab plus FOLFIRI therapy 
      and worse OS (grade 1-2, HR 0.96 [95% CI 0.76-1.20]; grade 3+, HR 2.72 [95% CI 
      1.67-4.44]; P = 0.001) and PFS (grade 1-2, HR 1.01 [95% CI 0.83-1.23]; grade 3+, 
      HR 2.22 [95% CI 1.43-3.45]; P = 0.005). No other AEs were significantly 
      associated with OS or PFS. CONCLUSIONS: Ramucirumab-induced hypertension was not 
      associated with improved OS and PFS in patients with mCRC treated with 
      ramucirumab and FOLFIRI, but severe diarrhea was associated with poorer OS and 
      PFS. CLINICAL TRIAL REGISTRATION: No. NCT01183780.
FAU - Lim, Huezin H
AU  - Lim HH
AUID- ORCID: 0000-0003-2888-6088
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, 
      Australia. lim0654@flinders.edu.au.
FAU - Hopkins, Ashley M
AU  - Hopkins AM
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, 
      Australia.
FAU - Rowland, Andrew
AU  - Rowland A
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, 
      Australia.
FAU - Yuen, Hoi Y
AU  - Yuen HY
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, 
      Australia.
FAU - Karapetis, Christos S
AU  - Karapetis CS
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, 
      Australia.
FAU - Sorich, Michael J
AU  - Sorich MJ
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 5042, 
      Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT01183780
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (KDR protein, human)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
RN  - IFL protocol
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse 
      effects/therapeutic use
MH  - Camptothecin/administration & dosage/adverse effects/analogs & derivatives
MH  - Colorectal Neoplasms/*drug therapy/mortality/pathology
MH  - Diarrhea/chemically induced/mortality/pathology
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Hypertension/chemically induced/mortality/pathology
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Neoplasm Metastasis
MH  - Prognosis
MH  - Randomized Controlled Trials as Topic
MH  - Survival Rate
MH  - Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
MH  - Ramucirumab
EDAT- 2019/11/05 06:00
MHDA- 2020/07/23 06:00
CRDT- 2019/11/03 06:00
PHST- 2019/11/05 06:00 [pubmed]
PHST- 2020/07/23 06:00 [medline]
PHST- 2019/11/03 06:00 [entrez]
AID - 10.1007/s11523-019-00683-z [pii]
AID - 10.1007/s11523-019-00683-z [doi]
PST - ppublish
SO  - Target Oncol. 2019 Dec;14(6):743-748. doi: 10.1007/s11523-019-00683-z.