In a nutshell
This study looked at abemaciclib (Verzenio), trastuzumab (Herceptin), and fulvestrant (Faslodex) for the treatment of advanced hormone-receptor-positive (HR+) and HER2 positive (HER2+) breast cancer. It found that this treatment led to better outcomes than standard-of-care chemotherapy for these patients.
Worldwide, breast cancer is the most commonly diagnosed cancer for women. Many breast cancers grow in response to the reproductive hormones estrogen and progesterone and are said to be HR+. 10% of breast cancer cases are positive for both HR and the growth factor HER2. Targeted therapies that act against HER2, including trastuzumab, have improved outcomes for this cancer. However, there are few effective options when the cancer has already been treated with two or more therapies.
Cyclin-dependent kinases (CDKs) are signaling molecules involved in cell multiplication and growth. Abemaciclib is a targeted therapy that inhibits two of these kinases, CDK4 and CDK6. Abemaciclib is effective in treating breast cancer which is HR+ and HER2-negative. A small initial trial found that abemaciclib may also be effective against HR+ and HER2+. It is not clear whether abemaciclib is an effective treatment for advanced HR+ and HER2+ breast cancer.
Methods & findings
This study included 237 patients with advanced HR+ and HER2+ breast cancer across 75 treatment centers. 118 patients (50%) had already received three or more treatments. All but five patients had previously received trastuzumab emtansine (Kadcyla). Groups A, B, and C were randomly assigned 79 patients each. Group A was treated with abemaciclib, trastuzumab, and fulvestrant (Faslodex). Group B received abemaciclib and trastuzumab, while group C received standard-of-care chemotherapy which might vary between treatment centers. Patients were followed for an average of 19.0 months.
Group A had a significantly longer average time before the cancer progressed (worsened) compared to group C (8.3 vs. 5.7 months). The average time before progression in group B (5.7 months) was not different from group C.
Low white blood cell count was the most common serious side effect (27% – group A, 22% – group B, and 26% – group C).
The bottom line
This study found that abemaciclib, trastuzumab, and fulvestrant led to better outcomes than standard-of-care chemotherapy for patients with advanced HR+ and HER2+ breast cancer. There was no advantage to abemaciclib plus trastuzumab without the third medication compared to chemotherapy.
The fine print
This study was funded by Eli Lily, the manufacturer of Verzenio.
Published By :
The Lancet. Oncology
Apr 27, 2020