Tyverb in combination with capecitabine for HER2+ metastatic breast cancer EGF100151 pivotal study

Final survival analysis of the EGF100151 study

Reference:
Cameron D, Casey M, Oliva C, et al. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomised trial.
The Oncologist. 2010;15:924–934.

Background:
Women with previously treated HER2+ locally advanced or metastatic breast cancer (MBC) who received Tyverb in combination with capecitabine achieved a longer time to progression (TTP) than those treated with capecitabine alone in this phase III registration trial. Since TPP was the primary endpoint of the trial, this prompted the early termination of patient enrolment. Interim data were reported in 2008, with updated and biomarker analyses also published the same year. Overall survival (OS) data were immature at this time.

Purpose:
To report mature OS data from the EGF100151 study.

Methods:

  • Phase III, multicentre, randomised, open-label trial.
  • A total of 408 women with HER2+ MBC were enrolled in the study, nine were being screened when study accrual was stopped and were offered combination treatment. All women had received prior anthracycline, taxane and trastuzumab-based regimens.
  • A total of 207 women received Tyverb (1250 mg/day) plus capecitabine (2000 mg/m2/day on Days 1–14 of a 21-day cycle) and 201 women received capecitabine monotherapy (2500 mg/m2/day on Days 1–14 of a 21-day cycle).
  • OS was a secondary endpoint of the trial.

Results:

  • At the time of the final survival analysis, 340 of the 408 patients (83%) had died.
  • Median OS was 75 weeks for the combination of Tyverb plus capecitabine versus 64.7 weeks for capecitabine monotherapy. The hazard ratio (HR) was 0.87, with a 95% confidence interval (CI) between 0.71 and 1.08 (P=0.210).
  • A total of 36 patients (17.9%) taking capecitabine monotherapy crossed over to combination treatment. When crossover was considered as a time-dependent covariate, a 20% lower risk for death was observed (HR=0.80, 95% CI 0.64–0.99; P=0.043).
  • The incidence of adverse events was consistent with those previously reported from the trial.

Conclusions:
These findings continue to support the clinical benefit and safety of Tyverb combined with capecitabine in patients with HER2+ metastatic breast cancer.

EGF100151: Safety and efficacy results

Reference: 1. Cameron D, Casey M, Oliva C, et al. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomised trial The Oncologist. 2010;15:924–934.