Terry L. Evans, MD
CDK4/6 inhibitors have been game-changing treatments for patients with hormone receptor (HR)–positive metastatic breast cancer, said Terry L. Evans, MD.
In the past, patients were treated with either exemestane or fulvestrant (Faslodex) as single agents, but research has shown that adding a CDK4/6 inhibitor to fulvestrant can improve progression-free survival (PFS) and clinical benefit rates in this population.
For example, data from the phase III PALOMA-3 trial, which were the basis for the FDA approval of palbociclib (Ibrance) in February 2016, demonstrated that the combination of the CDK4/6 inhibitor palbociclib with fulvestrant led to a clinically meaningful benefit in overall survival (OS) in patients with HR-positive, HER2-negative advanced breast cancer who progressed or relapsed on prior endocrine therapy.
At a median follow-up of 44.8 months in the intent-to-treat population, the combination led to a median OS improvement of 6.9 months compared with fulvestrant plus placebo (stratified hazard ratio, 0.81; 95% CI, 0.64-1.03; 1-sided P
= .043). The median OS with the combination was 34.9 months (95% CI, 28.8-40.0) compared with 28.0 months (95% CI, 23.6-34.6) with fulvestrant/placebo.
In addition to palbociclib, abemaciclib (Verzenio) and ribociclib (Kisqali) are 2 other CDK4/6 inhibitors available to treat patients with HR-positive, HER2-negative advanced breast cancer.
In September 2017, the FDA initially approved abemaciclib in combination with fulvestrant for patients with HR-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy. It was simultaneously approved as a monotherapy for those with this breast cancer subtype who previously received endocrine therapy and chemotherapy. In February 2018, abemaciclib was approved for use in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer.
Frontline ribociclib was approved by the FDA in July 2018 for use in combination with an AI for the treatment of pre-, peri-, or postmenopausal women with HR-positive/HER2- negative advanced or metastatic breast cancer, and for use in combination with fulvestrant for the treatment of postmenopausal women with this subtype of advanced or metastatic breast cancer, in the frontline setting or after disease progression on endocrine therapy. This regulatory decision follows ribociclib’s initial approval in March 2017 for treatment of postmenopausal women with HR-positive, HER2- negative advanced or metastatic breast cancer in combination with an AI as initial endocrine therapy.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Breast Cancer, Evans, a medical oncologist and clinical assistant professor of medicine at the University of Pittsburgh Medical Center, discussed the impact of CDK4/6 inhibitors in the metastatic breast cancer space and challenges that still need to be addressed.
OncLive: Please provide an overview of your presentation.
: My presentation addressed an important clinical scenario that we all face day-to-day in our practices: what to do with estrogen receptor–positive, postmenopausal patients when their disease progresses. The 3 trials that I discussed are the PALOMA-2, MONALEESA-2, and MONARCH 3 trials, which looked at the use of 3 CDK4/6 inhibitors in combination with an AI. All the trials basically showed the same PFS advantage, with hazard ratios in the 0.55 range, so it seems that they are all equally effective.
Is there an optimal partner for each of these CDK4/6 inhibitors?
I don’t think it matters. All of the trials used letrozole or anastrozole [as partner drugs]; I don’t think there’s any difference. In MONALEESA-7, the premenopausal study, everybody had to receive goserelin monthly and then investigators paired it either with tamoxifen, letrozole, or anastrozole, and it seemed to make no difference what the partner drug was.