Dr Rosen on the Activity of Zotatifin Plus Abemaciclib/Fulvestrant in ER+ Breast Cancer

Ezra Rosen, MD, PhD, breast oncologist, early drug development specialist, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the investigation of the triplet combination of zotatifin (eFT226), abemaciclib (Verzenio), and fulvestrant (Faslodex) in a phase 1/2 trial (NCT04092673) in heavily pretreated patients with estrogen receptor (ER)–positive metastatic breast cancer.

At the 2023 ASCO Annual Meeting, investigators presented data from the dose-expansion study, demonstrating that the triplet produced an unconfirmed overall response rate (ORR) of 26%, including 4 confirmed partial responses and 1 unconfirmed partial response.

This trial evaluated 2 expansion cohorts of patients on the phase 1/2 study, including patients that either received zotatifin plus fulvestrant (n = 18) or the triplet of fulvestrant, abemaciclib, and zotatifin (n = 20).

Safety outcomes for the triplet were a significant area of interest entering the study, Rosen notes. However, zotatifin demonstrated tolerability in combination with abemaciclib and fulvestrant, Rosen says.

Most the most common any-grade treatment-emergent adverse effects (AE) included diarrhea, nausea, vomiting, fatigue, dysgeusia, dry mouth, abdominal pain, anemia, dyspnea, and peripheral neuropathy. Notably, fatigue was typically observed within the first 24 hours after patients received an infusion of zotatifin, after which the AE generally resolved, Rosen explains. Nausea was controlled with standard-of-care treatments and antiemetics, Rosen concludes.