PMID- 32201506
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 12
DP  - 2020
TI  - Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in 
      metastatic colorectal cancer: results of the phase II North Central Cancer 
      Treatment Group study N054C (Alliance).
PG  - 1758835920910913
LID - 10.1177/1758835920910913 [doi]
LID - 1758835920910913
AB  - BACKGROUND: Bevacizumab (BEV), a monoclonal antibody against vascular endothelial 
      growth factor-A (VEGF-A), is a standard component of medical therapy of 
      metastatic colorectal cancer (mCRC). Activation of alternative angiogenesis 
      pathways has been implicated in resistance to BEV. This phase II study examines 
      the activity of combined vertical blockade of VEGF signaling with sorafenib and 
      BEV as salvage therapy in patients with progressive disease (PD) on all standard 
      therapy in mCRC. METHODS: mCRC patients with documented PD on standard therapy, 
      received sorafenib (200 mg orally twice daily, days 1-5 and 8-12) and BEV 
      (5 mg/kg intravenously, day 1) every 2 weeks. Primary endpoint was 3-month 
      progression-free survival (PFS) rate and secondary endpoints were overall 
      survival (OS), response rate (RR), safety, and feasibility. RESULTS: Of the 83 
      patients enrolled, 79 were evaluable. Of these, 42 (53%) were progression-free at 
      3 months. Median PFS was 3.5 months and median OS was 8.3 months. One patient had 
      a partial response and 50 patients (63.3%) had at least one stable tumor 
      assessment. Of 79 evaluable patients, 54 (68%) experienced grade 3/4 adverse 
      events (AEs) at least possibly related to treatment. Most frequent grade 3/4 AEs 
      were: fatigue (24.1%), hypertension (16.5%), elevated lipase (8.9%), hand-foot 
      skin reaction (8.9%), diarrhea (7.6%), and proteinuria (7.6%). Reasons for 
      treatment discontinuation were PD (72%), AEs (18%), patient refusal (8%), 
      physician decision (1%), and death (1%). CONCLUSIONS: The combination of BEV and 
      sorafenib as salvage therapy in heavily pretreated mCRC patients is tolerable and 
      manageable, with evidence of promising activity. CLINICALTRIALSGOV IDENTIFIER: 
      NCT00826540, URL:http://clinicaltrials.gov/ct2/show/NCT00826540.
CI  - (c) The Author(s), 2020.
FAU - Xie, Hao
AU  - Xie H
AUID- ORCID: 0000-0002-9640-4055
AD  - Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
FAU - Lafky, Jacqueline M
AU  - Lafky JM
AD  - Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA Department 
      of Biostatistics, Mayo Clinic, Rochester, MN, USA.
FAU - Morlan, Bruce W
AU  - Morlan BW
AD  - Department of Biostatistics, Mayo Clinic, Rochester, MN, USA.
FAU - Stella, Philip J
AU  - Stella PJ
AD  - St Joseph Mercy Health System, Ann Arbor, MI, USA.
FAU - Dakhil, Shaker R
AU  - Dakhil SR
AD  - Wichita Community Clinical Oncology Program, Wichita, KS, USA.
FAU - Gross, Gerald G
AU  - Gross GG
AD  - MeritCare Health System, Fargo, ND, USA.
FAU - Loui, William S
AU  - Loui WS
AD  - University of Hawaii Cancer Center, Honolulu, HI, USA.
FAU - Hubbard, Joleen M
AU  - Hubbard JM
AD  - Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
FAU - Alberts, Steven R
AU  - Alberts SR
AD  - Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
FAU - Grothey, Axel
AU  - Grothey A
AD  - Medical Oncology, West Cancer Center, 9745 Wolf River Blvd, Germantown, TN 
      38138-1762, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00826540
GR  - U10 CA180821/CA/NCI NIH HHS/United States
GR  - U10 CA180882/CA/NCI NIH HHS/United States
GR  - UG1 CA189808/CA/NCI NIH HHS/United States
GR  - UG1 CA232760/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20200306
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC7066587
OTO - NOTNLM
OT  - antiangiogenesis
OT  - bevacizumab
OT  - colorectal cancer
OT  - single nucleotide polymorphism
OT  - sorafenib
COIS- Conflict of interest statement: The Mayo Clinic Foundation received funding for 
      research activities carried out by A. Grothey from Genentech/Roche and Bayer 
      Oncology. All remaining authors have declared no conflicts of interest.
EDAT- 2020/03/24 06:00
MHDA- 2020/03/24 06:01
PMCR- 2020/03/06
CRDT- 2020/03/24 06:00
PHST- 2019/03/21 00:00 [received]
PHST- 2020/01/20 00:00 [accepted]
PHST- 2020/03/24 06:00 [entrez]
PHST- 2020/03/24 06:00 [pubmed]
PHST- 2020/03/24 06:01 [medline]
PHST- 2020/03/06 00:00 [pmc-release]
AID - 10.1177_1758835920910913 [pii]
AID - 10.1177/1758835920910913 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2020 Mar 6;12:1758835920910913. doi: 
      10.1177/1758835920910913. eCollection 2020.