(CHICAGO, IL) – Taxane-based chemotherapy plus lapatinib is associated with a shorter progression-free survival (PFS) than when combined with trastuzumab as first-line treatment for patients with HER2+ metastatic breast cancer, according to an interim analysis of an open-label Phase 3 randomized study presented at the 2012 American Society of Clinical Oncology Annual Meeting.

Lapatinib has not previously been directly compared to trastuzumab in the first-line metastatic setting. This open-label 24-week trial compared paclitaxel (80mg/m2 IV once weekly) or docetaxel (75mg/m2 IV 3 times weekly) in combination with lapatinib (1,250mg orally daily) or trastuzumab (2mg/kg IV once weekly or 6mg/kg IV three times weekly) after a loading dose, said lead study author Karen A. Gelmon, MD, of the British Columbia Cancer Agency-Vancouver Cancer Centre, Vancouver, BC, Canada.

Stratification was by prior neo/adjuvant HER2 therapy, prior neo/adjuvant taxane-based chemotherapy, planned taxane-based chemotherapy (paclitaxel vs docetaxel), and liver metastases.

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Between July 17, 2008, and December 1, 2011, 652 patients were accrued; data from 636 were included in the interim analysis with a clinical cutoff date of November 7, 2011, and database lock of April 13, 2012. Median follow-up was 13.6 months, 12.9 months for the lapatinib arm and 14.0 months for the trastuzumab arm.

The intent-to-treat (ITT) analysis included 318 patients in the lapatinib arm (266 with centrally confirmed HER2/neu status) and 318 in the trastuzumab arm (259 centrally confirmed). Median age was 55.4 years in the lapatinib arm and 54.1 years in the trastuzumab arm; 18% in each arm had received prior neo/adjuvant anti HER2/neu therapy.

The protocol-specified interim analysis was performed after 333 progression-free survival (PFS) events, with the trial to stop if the 2-sided P-value from the stratified log-rank test was <0.03, Dr. Gelmon said. The NCIC CTG’s independent data safety monitoring committee reviewed the interim analysis data and recommended disclosure, noting the superiority boundary had been crossed.

In the ITT analysis, PFS was 11.4 months in the trastuzumab arm and 8.8 months in the lapatinib arm (HR 1.33 [95% CI 1.06–1.67]; P=0.01). In patients with centrally confirmed HER2+ disease, median PFS was 13.7 months in the trastuzumab arm and 9.0 months in the lapatinib arm (HR 1.48; [95% CI 1.15–1.92]; P=0.003).

No difference in overall survival was detected between the two arms (HR 1.1 [95% CI 0.75–1.61]; P=0.62), including utilizing the centrally confirmed HER2+ analysis (HR 1.25 [95% CI 0.81-1.93]; P=0.32).

The toxicity pattern of the two arms was different, Dr. Gelmon said, with more rash and diarrhea in the lapatinib arm and a higher incidence of decrease in LVEF from baseline in the trastuzumab arm.

She noted that future analysis of these trial data will include a focus on the incidence of brain metastasis as site of first recurrence, treatment exposure, response rate, quality of life, and correlative studies.