|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
According to results of a phase 2 PREDIX HER2 study (ClinicalTrials.gov Identifier #: NCT02568839), patients with HER2-positive, hormone receptor-positive stage II/III breast cancer had similar rates of pathologic complete response (pCR) and less toxicity when treated with neoadjuvant trastuzumab emtansine (T-DM1) compared with a neoadjuvant chemotherapy-based regimen containing both pertuzumab and trastuzumab,. The findings from this study were presented at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, IL.
Neoadjuvant therapy is a standard of care in patients with HER2-positive, stage II/III operable breast cancer. While neoadjuvant regimens including 2 anti-HER2 targeted agents in combination with chemotherapy have achieved high pathologic complete response (pCR) rates, toxicity due to chemotherapy can be considerable. A regimen including trastuzumab emtansine (T-DM1) may represent an effective alternative treatment in this setting, although the possible existence of tumor HER2 heterogeneity could mitigate its potential benefits.
This randomized, open-label clinical trial randomly assigned (1:1) 202 patients with operable HER2-positive breast cancer characterized by tumors >20 mm or verified lymph node metastasis to receive neoadjuvant therapy with 6 cycles of either T-DM1 or the regimen of docetaxel, trastuzumab and pertuzumab. Crossover was allowed for nonresponding patients or those experiencing severe treatment-related toxicity. Adjuvant chemotherapy consisted of epirubicin/cyclophosphamide followed by trastuzumab (2 cycles in the arm receiving neoadjuvant docetaxel/trastuzumab/pertuzumab and 4 cycles in the neoadjuvant T-DM1 arm), radiotherapy, and endocrine therapy, when appropriate.
The median age of the study population was 52 years, and 62.6% of the tumors were classified as hormone receptor- (HR-) positive. Clinicopathologic characteristics related to menopausal status, and tumor stage were well balanced between the 2 study arms.
The rate of pathologic complete response (pCR) were 47% and 45% for patients receiving T-DM1 and docetaxel/trastuzmab/pertuzumab, respectively (P = .359).
Of note, lower pCR rates were observed for patients with HR-positive tumors; these were 36%, and 36% in the T-DM1,and docetaxel/trastuzmab/pertuzumab arms, respectively (P =.929).
In contrast, the corresponding pCR rates for patients with HR-negative tumors were 57%, and 67% for the groups receiving T-DM1 and docetaxel/trastuzmab/pertuzumab, respectively (P =.502).
The pCR rate was independent of tumor size for both regimens, and rates of breast-conserving therapy were 47% and 48% in patients receiving T-DM1-based therapy compared with chemotherapy-based treatment.
Regarding rates of grade 3/4 adverse events, febrile neutropenia (23% versus 3%), infection (11% versus 1%), and diarrhea (14% versus 0%) were substantially higher in patients receiving the docetaxel-containing regimen.
In his concluding comments, Dr Jonas Bergh, the study presenter, stated that “there were no statistically significant differences in pCR rates between docetaxel/trastuzumab/pertuzumab versus T-DM1.“
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- Bergh JCS, Andersson A, Bjohle J, et al. Docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer: Results from the Swedish PREDIX HER2 trial identifying a new potential de-escalation standard? Presented at: 2019 American Society of Clinical Oncology. May 31-June 4, 2019; Chicago, IL: Abstract 501.