Possible Alternative Therapy Found for Certain Breast Cancers

A recent trial showed that T-DM1 treatment with or without endocrine therapy may be a safe and effective alternative to standard chemotherapy plus trastuzumab in patients with HER2-positive/hormone receptor (HR)-negative cancer.

HER2-positive/HR-positive breast cancer is associated with lower sensitivity to chemotherapy and slightly better outcomes, compared with HER2-positive/HR-negative cancer.
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In the ADAPT trial, the researchers evaluated a total of 375 patients with early HER2-positive/HR-positive breast cancer. Patients were randomly assigned to receive either 12 weeks of T-DM1, with or without endocrine therapy, or to trastuzumab with endocrine therapy (129 patients). According to the researchers, patient characteristics were similar across groups.

A total of 127 patients received 12 weeks of T-DM1 with endocrine therapy, 119 received T-DM1 without endocrine therapy, and 129 received trastuzumab with endocrine therapy. Results indicated that 41.5% of patients receiving T-DM1 plus endocrine therapy demonstrated pathologic complete response, compared with 41% of the patients receiving T-DM1 without endocrine therapy and 15.1% of the patients receiving trastuzumab plus endocrine therapy.

The researchers deemed about two-thirds (67.1%) of patients as early responders, based on changes in Ki-67 level or low cellularity of tumors. Early responders were significantly more likely to achieve pathologic complete responses (35.7%), compared with non-responders (19.8%).

Toxicity was similar in both T-DM1 groups, according to the researchers. A total of 7.5% of patients in both T-DM1 groups had at least 1 adverse event that was grade 3 or higher, versus 4.1% of trastuzumab patients. The most commonly reported adverse events were increases in transaminases.

No new T-DM1 safety signals were found in the study, the researchers noted.

“In summary, only 4 cycles of neoadjuvant T-DM1 in HER2-positive/HR-positive early breast cancer yield substantial pathologic complete response rates- quite comparable to standard chemotherapy plus trastuzumab (or even to dual HER2 blockade),” the researchers concluded. “T-DM1 may be an efficient and safe alternative for patients who are not suited for systemic chemotherapy in this setting; the addition of endocrine therapy does not seem to play a crucial role.”

—Christina Vogt

Reference:

Harbeck N, Gluz O, Christgen M, et al. De-escalation strategies in human epidermal growth factor receptor 2 (Her2)–positive early breast cancer (BC): final analysis of the west German study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC Her2- and hormone receptor–positive phase II randomized trial—efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET [published online July 6, 2017]. JCO. DOI: 10.1200/JCO.2016.71.9815.