Treating Advanced Breast Cancer in Community Settings - Episode 7
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The FDA approved pertuzumab plus trastuzumab and chemotherapy as a neoadjuvant treatment for patients with HER2-positive early stage breast cancer in September 2013. This approval was based on findings from the phase II NeoSphere trial, which showed that pertuzumab combined with trastuzumab and docetaxel significantly improved pathologic complete response (pCR) when compared with other neoadjuvant regimens.
An improvement in pCR in the neoadjuvant setting often predicts benefit in the adjuvant setting, notes Hope S. Rugo, MD. As a result, the NCCN guidelines have incorporated the use of pertuzumab as an adjuvant therapy. However, the predicted value of pCR has recently been called into question, as a result of findings from the ALTTO trial, suggests Adam M. Brufsky, MD, PhD.
In the ALTTO study, the combination of lapatinib and trastuzumab as an adjuvant treatment for women with early breast cancer failed to demonstrate a significant improvement in disease-free survival over standard. These findings came as a contradiction to findings from the NeoALTTO study, which showed that patients who achieved a pCR after receiving the two drugs as neoadjuvant therapy displayed a significantly higher rate of 3-year event-free survival.
Different combinations were utilized in the NeoSphere and NeoALTTO, Sara Hurvitz, MD, explained, while cautioning against cross-study comparisons. Many of the patients on the ALTTO study required dose reductions with the combination of lapatinib and trastuzumab, which could have impacted the efficacy of the combination, Hurvitz notes.
The bar may have been set too high for the combination of lapatinib and trastuzumab in the adjuvant setting, suggests Eleftherios Mamounas, MD. Findings from the ALTTO study, as they relate to pCR, appear to be an anomaly, when looking at findings from other studies. Across the board, pCR has consistently correlated with survival and improved outcomes in the adjuvant setting across several studies, notes Mamounas.
The I-SPY trial is exploring several targeted therapies in combination with a standard taxane/anthracycline backbone for patients with breast cancer in the neoadjuvant setting, notes Rugo. In the study, patients are stratified based on cancer subtype and molecular profile to receive a treatment that is tailored to their individual biology. Drug combinations that demonstrate a favorable pCR rate within a distinct population in the first portion of the study will be explored in a larger phase III study, Rugo notes. In this example, pCR is being utilized to speed the pace of new drug discovery.