Dr. Lisa Carey authors editorial on neoadjuvant trials for breast cancer

Lisa Carey, MD, authored an editorial, titled “Neoadjuvant Trials of Human Epidermal Growth Factor Receptor 2 Targeting: How Many Drugs Do We Need?”

The editorial appeared in the June 1 issue of the Journal of Clinical Oncology.

Dr. Carey is the Richard and Marilyn Jacobs Preyer Distinguished Professor of Breast Cancer Research and Associate Director of Clinical Research for UNC Lineberger.

“Neoadjuvant” therapy means that the medical therapy (for example chemotherapy or biologic therapy) is given before surgery, when the tumor is still present in the breast so the response to treatment can be measured directly.  She outlined several reasons for the intense interest in neoadjuvant trials: 1) compared with adjuvant (postoperative treatment) trials, neoadjuvant trials are smaller and give results in months, not years; 2) they provide fertile ground for genetic and molecular efforts to figure out why some tumors respond and others do not; and 3) because we can measure the tumor growth or shrinkage during the course of the trial, the trial can be adapted in real-time  in a way that adjuvant studies cannot.

Dr. Carey’s editorial focused on a recent series of neoadjuvant trials examining the benefits of attacking the human epidermal growth factor receptor 2 (HER2) protein using HER2-targeted drugs.   Each trial used chemotherapy to which was added HER2- targeted drugs either one at a time or two together. The drugs included lapatinib, trastuzumab, or pertuzumab.   In all of the studies she described, chemotherapy plus dual HER2 targeting outperformed chemotherapy plus a single HER2-directed agent.  The only oral drug, lapatinib, was less effective and had more side effects when used by itself compared with the other drugs; she predicted that this drug will no longer be studied alone.   Dr. Carey is the lead investigator of a recently completed NCI-sponsored national cooperative group trial that actually allows doctors to limit the chemotherapy component of the treatment if the tumor responds extremely well to the HER2-targeted part of the treatment. This is one step towards what all doctors and patients want – personalized medicine.

Dr. Carey stated, “It is likely that future generations of trials in HER2-positive disease will now include dual targeting as the norm.”

She also posed a question, asking, “Paradoxically, the need now is for these studies to help us tailor therapy more thoughtfully- do we really believe that all HER2-positive breast cancers need multiple HER2-targeted agents?” She added that the laboratory studies within the clinical trials will be key to developing truly personalized therapy; scientific discovery requires equal commitment to the biologic questions and the clinical ones.”

Dr. Carey concluded that “we can and should use the neoadjuvant studies to help us more carefully choose the question, the trial design, and the patient population.”