Anthracycline/taxane regimens remain a standard of care for high-risk disease, and [docetaxel/cyclophosphamide] can be considered in low-risk patients or in those with significant cardiac risk factors.— Sara M. Tolaney, MD, MPH
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ASCO has published an adaptation of the 2015 Cancer Care Ontario (CCO) clinical practice guideline on adjuvant chemotherapy for early-stage breast cancer.1 There were several areas of controversy that the guideline attempts to address.
Should Anthracyclines Be Standard of Care?
The guideline supports the use of anthracycline- and taxane-based therapy for higher-risk disease. It also suggests that, for HER2-negative disease, when an anthracycline is not preferred, docetaxel/cyclophosphamide (TC) for four cycles or cyclophosphamide/methotrexate/fluorouracil (CMF) for six cycles is an alternative to doxorubicin/cyclophosphamide (AC).
For HER2-positive disease, the guideline recommends trastuzumab (Herceptin) plus chemotherapy in patients with node-positive disease or tumors > 1 cm. Either docetaxel/carboplatin/trastuzumab or AC followed by taxane/trastuzumab is a reasonable approach for higher-risk HER2-positive disease, based on data from the Breast Cancer International Research Group (BCIRG) 006 study.2
At the time this guideline was published, data had not been available from the ABC (Anthracyclines in Early Breast Cancer) adjuvant trials.3 These studies were analyzed together and compared anthracycline/taxane regimens with six cycles of TC. They demonstrated that TC was not as effective as the anthracycline/taxane regimens, with a hazard ratio of 1.23 favoring the use of anthracyclines. The benefit was greatest within hormone receptor–negative and node-positive patients. Given these data, anthracycline/taxane regimens remain a standard of care for high-risk disease, and TC can be considered in low-risk patients or in those with significant cardiac risk factors.
Should Patients With T1abN0 HER2-Positive Tumors Receive Therapy?
For patients with node-negative tumors that are < 1 cm, the guideline states that trastuzumab plus chemotherapy can be considered. Since there are limited data available for this population from the pivotal adjuvant trials, the ASCO panel believes the decision for therapy in this group should be individualized. Data from two phase II studies for this population suggest that recurrences are rare in patients treated with chemotherapy and trastuzumab. The APT trial looked at treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy; the investigators found that the 4-year disease-free survival was 98.7%.4 Another trial looked at treatment with docetaxel/cyclophosphamide/trastuzumab and demonstrated that for patients with node-negative tumors, the 2-year disease-free survival was 98.1%.5 Given the excellent results seen in these trials, many physicians are treating patients with HER2-positive tumors < 1 cm (particularly those with T1b tumors), despite the lack of data from randomized clinical trials, as we know from historical data in untreated patients that the risk of recurrence for this population may be as high as 10% to 20%.6,7
Should Pertuzumab Be Used in the Adjuvant Setting?
The guideline notes that pertuzumab (Perjeta) received accelerated approval by the U.S. Food and Drug Administration (FDA) in 2013 for use in the preoperative setting, based on the results of two clinical trials showing improvement in pathologic complete response with the addition of pertuzumab.8,9
At this time, the guidelines do not recommend the routine use of platinum therapy in patients receiving preoperative or adjuvant chemotherapy for triple-negative breast cancer.— Sara M. Tolaney, MD, MPH
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Data are not yet available from the already enrolled adjuvant trial, which randomized patients to receive chemotherapy with or without pertuzumab (APHINITY). If these data demonstrate improved outcomes with pertuzumab, the FDA will likely grant pertuzumab full approval. Currently, the National Comprehensive Cancer Network Guidelines® support the use of pertuzumab in the adjuvant setting. This differs from the ASCO guideline adaptation, which neither recommends nor dissuades from the use of pertuzumab.
Should Patients With Triple-Negative Breast Cancer Receive Carboplatin?
Although preoperative trials have demonstrated that adding platinum therapy to an anthracycline-and-taxane backbone improves pathologic complete response, these studies were not powered to evaluate survival outcomes and also noted higher rates of treatment discontinuation and myelosuppression.10,11 At this time, the guideline does not recommend the routine use of platinum therapy in patients receiving preoperative or adjuvant chemotherapy for triple-negative breast cancer and rather recommend awaiting results of the ongoing trial that is evaluating this question (NRG-BR003). ■
Disclosure: Dr. Tolaney has received research funding from Genentech, Exelixis, Lilly, Novartis, Merck, and Pfizer.
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