Yelena Novik, MD
FDA approvals of the 3 novel CDK4/6 inhibitors– palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) have given oncologists a tool in their armamentarium against metastatic estrogen receptor (ER)-positive breast cancer, according to Yelena Novik, MD.
State of the Science Summit™ on Breast Cancer, Novik, associate professor, NYU Langone’s Perlmutter Cancer Center, discussed the application of CDK4/6 inhibition and methods to overcome resistance in ER-positive breast cancer.
OncLive: Please provide an overview of your presentation.
: We discussed overcoming hormone resistance in the treatment of [patients with] advanced and metastatic breast cancer. Over the last few years, we've been lucky to have access to new targeted agents of cell-cycle inhibitors. Currently, we have 3 FDA-approved agents–palbociclib, ribociclib, and abemaciclib. They have been shown in randomized controlled studies to be superior to hormonal agents in improving PFS, as well as responses in women with advanced breast cancer.
I discussed the PALOMA, MONALEESA, and MONARCH randomized studies. PALOMA-2 compared palbociclib versus placebo in combination with letrozole. MONALEESA-3 combined ribociclib versus placebo. MONARCH 2 examined abemaciclib versus placebo in both the first-line and second-line treatment of metastatic breast cancer with fulvestrant. These drugs work through the D1 cycle mechanism to significantly improve PFS in advanced breast cancer. We are very lucky to be able to offer these options to our patients.
What is the impact of the MONALEESA-7 trial?
Most of the trials in advanced breast cancer specifically target women who are menopausal or postmenopausal. It's much more difficult to conduct trials that specifically target premenopausal women. The MONALEESA-7 trial was directed to premenopausal women.
Premenopausal women were randomized to receive either hormonal therapy alone–which is ovarian suppression and either tamoxifen or an AI–or the combination of hormonal therapy and ribociclib. The women were followed for a number of years and followed for PFS as well as overall responses. Not surprisingly, the PFS was significantly superior in the combination group with ribociclib compared with standard therapy.
Are there any preemptive means of overcoming resistance?
Now that we have the FDA approval of those first-line therapies, we can offer them to women at the first presentation of metastatic disease. However, a patient who presents with advanced cancer may already have resistance. We are also studying these agents in adjuvant trials, so we may be able to potentially increase the time before metastatic disease can develop.
... to read the full story