PMID- 20606083
OWN - NLM
STAT- MEDLINE
DCOM- 20100818
LR  - 20220227
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 22
DP  - 2010 Aug 1
TI  - Phase II, open-label study of pazopanib or lapatinib monotherapy compared with 
      pazopanib plus lapatinib combination therapy in patients with advanced and 
      recurrent cervical cancer.
PG  - 3562-9
LID - 10.1200/JCO.2009.26.9571 [doi]
AB  - PURPOSE: Pazopanib and lapatinib are tyrosine kinase inhibitors that target 
      vascular endothelial growth factor receptor, platelet-derived growth factor 
      receptor, and c-Kit or epidermal growth factor receptor (EGFR) and human 
      epidermal growth factor receptor 2 (HER2/neu), respectively. In cervical cancer, 
      EGFR and HER2/neu overexpression and high microvascular density correlate with 
      survival. PATIENTS AND METHODS: Patients with measurable stage IVB 
      persistent/recurrent cervical carcinoma not amenable to curative therapy and at 
      least one prior regimen in the metastatic setting were randomly assigned in a 
      ratio of 1:1:1 to pazopanib at 800 mg once daily, lapatinib at 1,500 mg once 
      daily, or lapatinib plus pazopanib combination therapy (lapatinib at 1,000 mg 
      plus pazopanib at 400 mg once daily or lapatinib at 1,500 mg plus pazopanib at 
      800 mg once daily). Therapy continued until progression or withdrawal because of 
      adverse events (AEs). Primary end point was progression-free survival (PFS), and 
      secondary end points were overall survival (OS), response rate (RR), and safety. 
      The futility boundary was crossed at the planned interim analysis for combination 
      therapy compared with lapatinib therapy, and the combination was discontinued. 
      RESULTS: Of 230 patients enrolled, 152 were randomly assigned to the monotherapy 
      arms: pazopanib (n = 74) or lapatinib (n = 78). Most patients (62%) had recurrent 
      cancer. Pazopanib improved PFS (hazard ratio [HR], 0.66; 90% CI, 0.48 to 0.91; P 
      = .013) and OS (HR, 0.67; 90% CI, 0.46 to 0.99; P = .045). Median OS was 50.7 
      weeks and 39.1 weeks and RRs were 9% and 5% for pazopanib and lapatinib, 
      respectively. The only grade 3 AE > 10% was diarrhea (11% pazopanib and 13% 
      lapatinib). Grade 4 AEs were 9% (lapatinib) and 12% (pazopanib). CONCLUSION: This 
      study confirms the activity of antiangiogenesis agents in advanced and recurrent 
      cervical cancer and demonstrates the benefit of pazopanib based on the prolonged 
      PFS and favorable toxicity profile.
FAU - Monk, Bradley J
AU  - Monk BJ
AD  - University of California Irvine Medical Center, Orange, CA 92868, USA. 
      bjmonk@uci.edu
FAU - Mas Lopez, Luis
AU  - Mas Lopez L
FAU - Zarba, Juan J
AU  - Zarba JJ
FAU - Oaknin, Ana
AU  - Oaknin A
FAU - Tarpin, Carole
AU  - Tarpin C
FAU - Termrungruanglert, Wichai
AU  - Termrungruanglert W
FAU - Alber, Jacquelyn A
AU  - Alber JA
FAU - Ding, Jie
AU  - Ding J
FAU - Stutts, Melissa W
AU  - Stutts MW
FAU - Pandite, Lini N
AU  - Pandite LN
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100706
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Indazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinazolines)
RN  - 0 (Sulfonamides)
RN  - 0VUA21238F (Lapatinib)
RN  - 7RN5DR86CK (pazopanib)
SB  - IM
CIN - J Clin Oncol. 2011 Dec 20;29(36):4845. PMID: 22084371
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/*administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Disease-Free Survival
MH  - Drug Delivery Systems
MH  - Female
MH  - Humans
MH  - Indazoles
MH  - Lapatinib
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Pyrimidines/*administration & dosage/adverse effects
MH  - Quinazolines/*administration & dosage/adverse effects
MH  - Recurrence
MH  - Retreatment
MH  - Sulfonamides/*administration & dosage/adverse effects
MH  - Uterine Cervical Neoplasms/*drug therapy/mortality
EDAT- 2010/07/08 06:00
MHDA- 2010/08/19 06:00
CRDT- 2010/07/08 06:00
PHST- 2010/07/08 06:00 [entrez]
PHST- 2010/07/08 06:00 [pubmed]
PHST- 2010/08/19 06:00 [medline]
AID - JCO.2009.26.9571 [pii]
AID - 10.1200/JCO.2009.26.9571 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Aug 1;28(22):3562-9. doi: 10.1200/JCO.2009.26.9571. Epub 2010 
      Jul 6.