Can the development of lapatinib-related rash predict breast cancer outcome?

This study investigated how the early development of a rash in treatment with lapatinib (Tykerb) impacts survival outcomes in breast cancer. This study concluded that early development of rash may indicate the patients who will benefit more from lapatinib.

Lapatinib is a drug which targets epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). HER2 and EGFR are receptors involved in cancer growth. Lapatinib is considered a key drug in managing HER2-positive breast cancer, particularly when the cancer has spread or when other treatments, such as  trastuzumab (Herceptin), have failed.

It has been shown that early rash development is associated a better chance of achieving a complete response to lapatinib as a first treatment. The impact of rash development on survival has not previously been investigated.

This study included 6098 patients with HER2-positive breast cancer. Patients were randomly assigned to treatment with trastuzumab, lapatinib, a sequence of the two or a combination of the two for the duration of 1 year. The average follow up time was 4.5 years.

A total of 3973 patients were included in the final analysis. 35% of these developed a rash within the first 6 weeks of treatment. In these patients disease free survival (DFS, time from treatment until disease return) improved by 13% compared to patients who did not develop a rash. Overall survival (OS, time from treatment until death from any cause) was improved by 37%.

Of the 2051 patients assigned to a combination of trastuzumab and lapatinib, 692 developed early rash. In these patients, DFS was improved by 28% and OS improved by 41% compared to patients treated only with trastuzumab.

The study concluded that the early development of a rash may indicate which patients will benefit more from lapatinib-based treatment.

The patients included in this trial were chosen on the basis of experiencing a specific side effect of treatment after they had been randomly assigned to the trial. For this reason some selection bias may be present in the results.