Treating Endocrine-Resistant Metastatic Breast Cancer

In September, the FDA approved amebaciclib (Verzenio), the latest drug to treat endocrine resistant metastatic breast cancer (MBC). In combination with fulvestrant (Faslodex), the results of the phase III, Monarch 2 trial showed an improvement in progression free survival (PFS). All the patients in the trial were hormone receptor positive and HER2 negative, as are all the enrollees in the trials noted here.

The most common side effect associated with amebaciclib is diarrhea. Another toxicity is neutropenia (low white-cell blood count). And fatigue was also drawback.

Researchers have been working hard to develop treatments for MBC that become resistant to anti-hormone treatments such as tamoxifen, aromatase inhibitors (AIs) and fulvestrant. Over the last several years, the FDA has approved exemestane (Affinitor) and palbociclib (Ibrance). This year besides amebaciclib, they have also given a green light to ribociclib (Kisqali) in combination with letrozole.

In the phase III, Monarch 3 trial, researchers showed that combining anastrozole (Arimidex) or letrozole (Femara) with amebaciclib improved PFS. The results were reported at the European Society of Medical Oncology in September, and researchers are now analyzing the data further.

Other research reported in late August brought good news that yet another drug therapy could be destined to treat MBC that is resistant to endocrine therapy. Z-endoxifen, which is a derivative of tamoxifen, showed promise and is now being compared with tamoxifen in a phase II study. The study is ongoing but not recruiting patients.

As they go forward, clinical trial investigators are combining therapies that are already FDA approved, such as fulvestrant and palbociclib in the Paloma-3 trial. The investigators expect to have the results of this phase III study in January 2018. Another such trial, which is a phase II study, is examining fulvestrant and ribociclib. That study is currently enrolling patients.

Other phase III trials looking at the efficacy of combining an already approved drug with an experimental drug include the SANDPIPER trial, which is looking at fulvestrant and taselisib, and the SOLAR-1 trial, which is studying exemestane and entinostat. SANDPIPER and SOLAR-1 are currently enrolling patients.

Some clinical trials are combining three drugs such as FDA-approved ribociclib, everolimus and exemestane in the phase III TRINITI-1 trial. And a phase I study is examining fulvestrant, palbociclib and erdafitinib (experimental compound). However, MBC patients are concerned about the potential toxicities that could result from combining three systemic therapies rather than only two.

The clinical trial list here is not exhaustive, and those living with MBC can look for others trials online at, and Some trial protocols may require a certain cancer cell alteration and/or over-amplification, but patients can get clarification from their oncologists by printing out a copy of a trial and bringing it to their next visit.

Information about some of the clinical trials noted in this story was taken from a presentation given by Dr. Ingrid Mayer at this year’s annual meeting of the American Society of Clinical Oncology in June. In her session, Dr. Mayer reported on the potential drivers of endocrine-resistant MBC, current therapies and future directions. She is co-leader and clinical trial director of the breast cancer research program and associate professor of hematology/oncology at Vanderbilt-Ingram Cancer Center of Vanderbilt University Medical Center in Nashville.

by Joan Mancuso