Is Breast Cancer Research Geared to Our Patients?

Martine Piccart-Gebhart, MD, PhD, Assesses Progress in HER2-Positive Breast Cancer

Roxanne Nelson, BSN, RN


April 18, 2016

Editor's Note: Amplification or overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15%-25% of breast cancers and is associated with aggressive tumors. With the US Food and Drug Administration approval of trastuzumab in 1998, the paradigm of treatment for many patients with HER2-positive breast cancer significantly shifted—from that of an aggressive cancer to a chronic disease. Martine Piccart-Gebhart, MD, PhD, in her presentation of the Susan G Komen Brinker Award Lecture at the San Antonio Breast Cancer Symposium, reviewed the progress made in the treatment of HER2-positive breast cancer and examined whether translational and clinical research is geared to the questions of greatest concern to patients.

Will Dual Blockade Achieve 4-Year DFS in 2017?

"We have an impressive arsenal of drugs available to treat breast cancer," said Dr Piccart-Gebhart, professor of oncology at the Université Libre de Bruxelles and director of medicine at the Jules Bordet Institute, in Brussels, Belgium. "And we have global consensus on the best way of sequencing these agents."

Treatment with trastuzumab has improved time to progression and survival rates and led to the clinical development of other agents, including pertuzumab, ado-trastuzumab emtansine (T-DM1), and lapatinib, as well as novel agents currently under exploration.

Survival in advanced HER2 breast cancer has improved dramatically, reaching 56 months in the CLEOPATRA study.

"Randomized clinical trials have shown robust survival with dual blockade in first-line treatment with pertuzumab and trastuzumab in combination with a taxane, and with the elegant antibody conjugate T-DM1 as second-line treatment," said Dr Piccart-Gebhart. "Survival in advanced HER2 breast cancer has improved dramatically, reaching 56 months in the CLEOPATRA study."[1]

The Breast Cancer International Group, a nonprofit organization for academic breast cancer research groups based in Brussels, Belgium, has also been working to bring these targeted drugs, either as single-agent or combination therapy, to the adjuvant setting as quickly as possible.

There are more than 18,000 women who are participating in three trials: the HERA trial,[2] which recruited 5102 patients in 43 months and is evaluating single HER2 blockade (trastuzumab) vs observation; the ALTTO trial,[3] which recruited 8381 patients in 49 months and is looking at dual HER2 blockade vs single HER2 blockade (trastuzumab with or without lapatinib); and the APHINITY trial,[4] which is also evaluating dual vs single blockade (trastuzumab with or without pertuzumab).

"Because ALTTO did not succeed in bringing lapatinib to the adjuvant setting in 2014, our standard of care remains trastuzumab and chemotherapy in early breast cancer," said Dr Piccart-Gebhart. "Of course, we hope that trastuzumab and pertuzumab will show superiority in 2017, in which case we might reach 4-year disease-free survival (DFS) rates in the range of 90%. This would represent a 12%-18% absolute improvement, in comparison to the 4-year control arms of adjuvant trials."


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