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

Selected inflammatory breast cancer research published in 2013

What is an abstract?
An abstract is a brief summary of a research article, thesis, review, conference proceeding, or any in-depth analysis of a particular subject and is often used to help the reader quickly ascertain the paper’s purpose. The abstract can convey the main results and conclusions of a scientific article but the full text article must be consulted for details of the methodology, the full experimental results, and a critical discussion of the interpretations and conclusions.

The abstract below is not edited. Read the free complete article on PubMed Central.

Cristofanilli, M., et al. (2013). A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer. Breast Cancer Research and Treatment, 137(2), 471-82. doi: 10.1007/s10549-012-2369-x.

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 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}, respectively; median PFS was 16.1 and 14.3 weeks, respectively. Grade =3 adverse events (AEs) were more frequent in the combination arm (71 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}) than in the lapatinib arm (24 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}, respectively) than in the lapatinib monotherapy arm (0 and 11 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}, 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 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}, 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 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381} of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 {8bc207927c4afa415a72514e5792f759a4b3193deaad217687baa4c0cbc37381}, 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.

Previous article: Next article: