FDG-PET Predicts Complete Response to Neoadjuvant Trastuzumab/Docetaxel in HER2-Positive Breast Cancer
In the French phase II AVATAXHER trial reported in The Lancet Oncology, Coudert et al found that 18F–fluorodeoxyglucose (FDG) positron-emission tomography (PET) predicted complete response to trastuzumab (Herceptin)/docetaxel neoadjuvant therapy and that adding bevacizumab (Avastin) in FDG-PET nonresponders improved achievement of complete response
In this open-label trial, 142women with early-stage HER2-positive breast cancer received two cycles of neoadjuvant docetaxel (100 mg/m2 intravenously [IV] every 3 weeks) plus trastuzumab (8 mg/kg IV every 3 weeks then 6 mg/kg IV every 3 weeks for the second course) between May 2010 and October 2012. FDG-PET was performed before the first and second cycles, with the change in standardized uptake value being used to predict pathologic complete response.
Patients predicted to be responders on FDG-PET continued to receive standard therapy. Those predicted to be nonresponders were randomly assigned 2:1 to receive four cycles of docetaxel (100 mg/m2 IV every 3 weeks) and trastuzumab (6 mg/kg IV every 3 weeks) plus bevacizumab (15 mg/kg IV every 3 weeks) or to continue on docetaxel plus trastuzumab alone. The primary endpoint was centrally assessed pathologic complete response according to the Chevallier classification.
Pathologic Complete Response Rates
Of the 142 patients, 69 (49%) were predicted by FDG-PET to be treatment responders after two cycles of treatment. The 73 predicted nonresponders were randomly assigned to the bevacizumab (n = 48) and no-bevacizumab groups (n = 25). Pathologic complete response occurred in 37 (53.6%, 95% confidence interval [CI] = 41.2%–65.7%) of the FDG-PET responders, 21 (43.8%, 95% CI = 29.5%–58.8%) of the nonresponders receiving bevacizumab, and 6 (24.0%, 95% CI = 9.4%–45.1%) of the nonresponders not receiving bevacizumab.
Toxicity
Rates of grade 3 or 4 adverse events were similar in the initial FDG-PET responder, bevacizumab, and no-bevacizumab groups, with the most common being neutropenia (6%, 11%, 12%), febrile neutropenia (1%, 6%, 4%), and myalgia (6%, 0%, 4%). Serious adverse events occurred in 6%, 21%, and 4%. No deaths occurred during the study.
The investigators concluded: “In patients with HER2-positive breast cancer, early PET assessment can help to identify non-responders to neoadjuvant docetaxel plus trastuzumab therapy. In these patients, the addition of bevacizumab can increase the proportion of patients achieving a pathological complete response. This potential new role for PET and the activity of bevacizumab in this setting need to be confirmed in larger phase 3 trials.”
Bruno Coudert, MD, of Centre Georges-Francois Leclerc, Dijon, is the corresponding author for The Lancet Oncology article.
The study was funded by Roche France. For full disclosures of the study authors, visit www.thelancet.com.
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