No Benefit Shown With Afatinib in HER2-Positive Breast Cancer With Progressive Brain Metastases
In the phase II LUX-Breast 3 trial reported in The Lancet Oncology, Cortés et al found that afatinib (Gilotrif) alone or combined with vinorelbine did not increase patient benefit vs investigator choice of treatment in patients with HER2-positive breast cancer and progressive brain metastases during or after treatment with trastuzumab (Herceptin), lapatinib (Tykerb), or both.
Study Details
In the open-label trial, conducted at 40 sites in Canada, Finland, France, Germany, Italy, Spain, South Korea, and the United States, 121 patients were randomly assigned to receive afatinib at 40 mg once daily (n = 40), afatinib at 40 mg/d plus intravenous (IV) vinorelbine at 25 mg/m2 once weekly (n = 38), or investigator choice of treatment (n = 43) in cycles of 3 weeks until disease progression, patient withdrawal, or unacceptable toxicity.
The primary endpoint was patient benefit at 12 weeks, defined as absence of central nervous system (CNS) or extra-CNS disease progression, no tumor-related worsening of neurologic signs or symptoms, and no increase in corticosteroid dose.
Benefit Rates and Toxicity
All patients discontinued study treatment before the data collection cutoff in October 2014. Patient benefit was achieved in 30.0% of the afatinib group (P = .37 vs investigator choice), 34.2% of the afatinib/vinorelbine group (P = .63), and 41.9% of the investigator choice group.
Grade 3 or 4 treatment-related adverse events occurred in 53% of the afatinib group, 81% of the afatinib/vinorelbine group, and 21% of the investigator choice group. The most common in the afatinib group was diarrhea (18%, 24%, 5%), and the most common in the afatinib/vinorelbine group was neutropenia (0%, 38%, 10%).
The investigators concluded: “Patient benefit with afatinib-containing treatments was not different from that in patients given investigator’s choice of treatments; however, adverse events were frequent and afatinib-containing treatments seemed to be less well tolerated. No further development of afatinib for HER2-positive breast cancer is currently planned.”
The study was funded by Boehringer Ingelheim.
Javier Cortés, MD, of Vall d’Hebron Institute of Oncology, Barcelona, Spain, is the corresponding author of The Lancet Oncology article.
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