Lapatinib (L) with paclitaxel compared to paclitaxel as first-line treatment for patients with metastatic breast cancer: A phase III randomized, doubleblind study of 580 patients.
Authors: Leo et al. Abstract #1011
Reviewer: Dr. Christine Simmons Date posted: June 21, 2007
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Treatment A (L + P)
Lapatinib (1500mg) + Paclitaxel (175 mg/m2)
R
Locally advanced inoperable or metastatic Breast cancer
Treatment B (Placebo + P) Placebo + Paclitaxel (175 mg/m2)
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RESULTS
Lapatinib + Paclitaxel Response Rate (%) Toxic Deaths (%) TTP 35.1% 2.7% Placebo + Paclitaxel 25.3% 0.6% No difference
p-value
p< 0.008 OR= 1.7
Toxicity analysis revealed increased levels of diarrhea and neutropenia in the Lapatinib arm. An unplanned subgroup analysis was performed on the Her2status unknown patients that were later found to be Her2positive. Results of this analysis revealed an improved RR with an odds ratio of 2.9 (p = 0.027) in this population.
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STUDY COMMENTARY
• This trial attempted to show an improvement in TTP by adding a targeted agent towards Her2neu to chemotherapy in metastatic breast cancer patients with Her2neu negative disease.
• Unfortunately, the results were negative and failed to show an improvement in response by addition of Lapatinib in the Her-2 negative MBC. • This draws into question either the relative role of erb-B1 in cell proliferation or the efficacy of Lapatinib in targeting this receptor, or both. Indeed Lapatinib has been studied as a single agent in Her2negative breast tumours previously with minimal response.
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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• There is no evidence to use lapatinib routinely in the treatment of Her2neu negative disease, its role in Her2positive disease has been documented previously
• There now appears to be efficacy of lapatinib in combination with chemotherapy in the her-2 positive patients in the first line setting. This however needs to be confirmed in a randomized phase III study.
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