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A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer.

Publication ,  Journal Article
Cristofanilli, M; Johnston, SRD; Manikhas, A; Gomez, HL; Gladkov, O; Shao, Z; Safina, S; Blackwell, KL; Alvarez, RH; Rubin, SD; Ranganathan, S ...
Published in: Breast Cancer Res Treat
January 2013

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.

Duke Scholars

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

January 2013

Volume

137

Issue

2

Start / End Page

471 / 482

Location

Netherlands

Related Subject Headings

  • Treatment Outcome
  • Sulfonamides
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Quinazolines
  • Pyrimidines
  • Oncology & Carcinogenesis
  • Middle Aged
  • Lapatinib
  • Inflammatory Breast Neoplasms
 

Citation

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Cristofanilli, M., Johnston, S. R. D., Manikhas, A., Gomez, H. L., Gladkov, O., Shao, Z., … Trudeau, M. E. (2013). A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer. Breast Cancer Res Treat, 137(2), 471–482. https://doi.org/10.1007/s10549-012-2369-x
Cristofanilli, Massimo, Stephen R. D. Johnston, Alexey Manikhas, Henry L. Gomez, Oleg Gladkov, Zhimin Shao, Sufia Safina, et al. “A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer.Breast Cancer Res Treat 137, no. 2 (January 2013): 471–82. https://doi.org/10.1007/s10549-012-2369-x.
Cristofanilli M, Johnston SRD, Manikhas A, Gomez HL, Gladkov O, Shao Z, et al. A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer. Breast Cancer Res Treat. 2013 Jan;137(2):471–82.
Cristofanilli, Massimo, et al. “A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer.Breast Cancer Res Treat, vol. 137, no. 2, Jan. 2013, pp. 471–82. Pubmed, doi:10.1007/s10549-012-2369-x.
Cristofanilli M, Johnston SRD, Manikhas A, Gomez HL, Gladkov O, Shao Z, Safina S, Blackwell KL, Alvarez RH, Rubin SD, Ranganathan S, Redhu S, Trudeau ME. A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer. Breast Cancer Res Treat. 2013 Jan;137(2):471–482.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

January 2013

Volume

137

Issue

2

Start / End Page

471 / 482

Location

Netherlands

Related Subject Headings

  • Treatment Outcome
  • Sulfonamides
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Quinazolines
  • Pyrimidines
  • Oncology & Carcinogenesis
  • Middle Aged
  • Lapatinib
  • Inflammatory Breast Neoplasms