Trial Opens Door to Future Treatments
for High-Risk Breast Cancer Patients

There are highs and lows in the pursuit of new drugs to treat breast cancer, but even the lows provide the valuable detail that might help inform the next breakthrough.

As the Australian principal investigator on the Penelope-B trial, Associate Professor Nicole McCarthy, says the information gained from the trial will provide a sound platform for testing new drugs to target remaining cancer cells in the breast with the hope of improving outcomes for women with high-risk, early-stage breast cancer.

“The strategy of chemo or some other treatment before surgery and follow-up post-surgery treatment for resistant disease remains good,” she says. “It’s just super disappointing that in this particular example it didn’t work.”

The Penelope-B trial studied the effects of adding a one-year course of palbociclib, a cell cycle inhibitor, to standard endocrine/hormone treatment (ET) for patients with hormone receptor positive (HR positive), human epidermal growth factor receptor 2 negative (HER2 negative) breast cancer, who were at high risk of the cancer recurring.

Approximately one third of patients who have remaining cancer in their breast following neoadjuvant (before surgery) chemotherapy and surgery, will experience a relapse. It was hoped that the addition of palbociclib, an inhibitor that has been shown to improve outcomes when given with ET in patients with metastatic or locally advanced HR positive, HER2 negative breast cancer, would also prove beneficial for this sub-type of at-risk patients. Unfortunately, this was not the case.

Penelope-B was a German-led clinical trial that involved 1,250 patients internationally. In Australia, it included 90 women from 16 institutions. Half the total participants received palbociclib and the remainder received a placebo. After a median follow-up of 42.8 months, it was found that palbociclib did not improve iDFS (invasive disease-free survival) compared with standard ET alone.

Associate Professor McCarthy says the questions raised by the trial will inform future trials. “Twelve months of palbociclib was probably not an adequate treatment time,” she says. “Though the PALLAS trial went for two years and it was also negative, so an even longer duration of therapy may be needed.”

Associate Professor McCarthy explains that in the future, molecular profiling of residual disease may allow for tailoring of drug treatment. “Penelope-B was more of a broad approach,” she says. “More specific, smaller trials will make up future studies.”

Publication

Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer – the Penelope-B trial Loibl, S., Marmé, F., Martin, M., Untch, M., Bonnefoi, H., Kim, S.-B., Bear, H., McCarthy, N., Melé Olivé, M., Gelmon, K., García-Sáenz, J., Kelly, C. M., Reimer, T., Toi, M., Rugo, H. S., Denkert, C., Gnant, M., Makris, A., Koehler, M., Huhnag-Bartelett, C., Frean, MJL., Colleoni, M., Werutsky, G., Seiler, S., Burchardi, N., Nekljudova, V., von Minckwitz, G. (2021). Journal of Clinical Oncology, 39(14), 1518–1530. https://doi.org/10.1200/JCO.20.03639