PMID- 23239151
OWN - NLM
STAT- MEDLINE
DCOM- 20130725
LR  - 20211203
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 137
IP  - 2
DP  - 2013 Jan
TI  - A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients 
      with HER2+ inflammatory breast cancer.
PG  - 471-82
LID - 10.1007/s10549-012-2369-x [doi]
AB  - This multi-center Phase II study evaluated lapatinib, pazopanib, and the 
      combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 
      1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or 
      lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease 
      progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed 
      with this dose combination in another study (VEG20007), Cohort 1 was closed. The 
      protocol was amended such that an additional 88 patients (Cohort 2) were 
      randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg, 
      lapatinib 1,000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, 
      respectively. The primary endpoint was overall response rate (ORR). Secondary 
      endpoints included duration of response, progression-free survival (PFS), overall 
      survival, and safety. In Cohort 1, ORR for the lapatinib (n = 38) and combination 
      (n = 38) arms was 29 and 45 %, respectively; median PFS was 16.1 and 14.3 weeks, 
      respectively. Grade >/=3 adverse events (AEs) were more frequent in the combination 
      arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions 
      due to AEs were also more frequent in the combination arm (45 and 53 %, 
      respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). 
      In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + 
      pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; 
      median PFS was 16.0, 16.0, and 11.4 weeks, respectively. In the lapatinib, 
      combination, and pazopanib therapy arms, grade >/=3 AEs were reported for 17, 50, 
      and 46 % of patients, respectively, and the incidence of discontinuations due to 
      AEs was 0, 24, and 23 %, respectively. The lapatinib-pazopanib combination was 
      associated with a numerically higher ORR but no increase in PFS compared to 
      lapatinib alone. The combination also had increased toxicity resulting in more 
      dose reductions, modifications, and treatment delays. Activity with single-agent 
      lapatinib was confirmed in this population.
FAU - Cristofanilli, Massimo
AU  - Cristofanilli M
AD  - MD Anderson Cancer Center, Houston, TX, USA. Massimo.Cristofanilli@fccc.edu
FAU - Johnston, Stephen R D
AU  - Johnston SR
FAU - Manikhas, Alexey
AU  - Manikhas A
FAU - Gomez, Henry L
AU  - Gomez HL
FAU - Gladkov, Oleg
AU  - Gladkov O
FAU - Shao, Zhimin
AU  - Shao Z
FAU - Safina, Sufia
AU  - Safina S
FAU - Blackwell, Kimberly L
AU  - Blackwell KL
FAU - Alvarez, Ricardo H
AU  - Alvarez RH
FAU - Rubin, Stephen D
AU  - Rubin SD
FAU - Ranganathan, Sulabha
AU  - Ranganathan S
FAU - Redhu, Suman
AU  - Redhu S
FAU - Trudeau, Maureen E
AU  - Trudeau ME
LA  - eng
GR  - UL1 RR024148/RR/NCRR NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121213
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Indazoles)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinazolines)
RN  - 0 (Sulfonamides)
RN  - 0VUA21238F (Lapatinib)
RN  - 7RN5DR86CK (pazopanib)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Diarrhea/chemically induced
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Indazoles
MH  - Inflammatory Breast Neoplasms/*drug therapy/metabolism/mortality
MH  - Lapatinib
MH  - Middle Aged
MH  - Pyrimidines/administration & dosage/adverse effects/therapeutic use
MH  - Quinazolines/administration & dosage/adverse effects/*therapeutic use
MH  - Receptor, ErbB-2/*metabolism
MH  - Sulfonamides/administration & dosage/adverse effects/therapeutic use
MH  - Treatment Outcome
PMC - PMC3539065
EDAT- 2012/12/15 06:00
MHDA- 2013/07/26 06:00
PMCR- 2012/12/13
CRDT- 2012/12/15 06:00
PHST- 2012/11/19 00:00 [received]
PHST- 2012/11/30 00:00 [accepted]
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2013/07/26 06:00 [medline]
PHST- 2012/12/13 00:00 [pmc-release]
AID - 2369 [pii]
AID - 10.1007/s10549-012-2369-x [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2013 Jan;137(2):471-82. doi: 10.1007/s10549-012-2369-x. 
      Epub 2012 Dec 13.