Addition of CDK4/6 Inhibitors to Faslodex Improves Survival in Breast Cancer Subgroup

The addition of a CDK4/6 inhibitor to treatment with Faslodex (fulvestrant) improved survival among women with hormone receptor (HR)-positive, human epidermal growth factor (HER)2-negative advanced breast cancer, according to results from two studies presented at the European Society of Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain.

In particular, the Monaleesa-3 study showed that Kisqali (ribociclib) plus Faslodex as a first- or second-line treatment improved survival in postmenopausal patients; while the Monarch 2, showed a statistically and clinically meaningful improvement in overall survival with Verzenio (abemaciclib) plus Faslodex in pre-, peri- and postmenopausal women patients with HR-positive HER2-negative advanced breast cancer resistant to hormonal therapy.

“The results of Monarch 2 nicely complement those reported in Monaleesa-3,” Dr. Nadia Harbeck, from the University of Munich, commented on the study in a press release issued by ESMO. “Abemaciclib is the third CDK4/6 inhibitor to show an overall survival benefit in advanced (hormone receptor-positive), HER2-(negative) breast cancer.”

“Together with the data we have seen before with palbociclib and ribociclib, these new data strengthen the argument that we should start treatment in the metastatic setting with a CDK4/6 inhibitor plus endocrine therapy because these drugs substantially improve patient outcomes compared to anti-hormonal treatment alone,” she added.

Monaleesa-3

In MONALEESA-3, researchers randomized 726 postmenopausal men and women with HR-positive, HER2-negative advanced breast cancer to received treatment with either Kisqali plus Faslodex or placebo.

The combination led to an approximate 28% reduction in the risk of death compared with placebo. Moreover, median overall survival was not reached in the Kisqali arm, compared with 40 months in the placebo group.

Moreover, the survival benefit was seen among women not previously treated with hormonal therapy as well as in those who had become resistant to endocrine therapy.

"This is a significant, practice-changing report, in that we are now saying that patients with advanced breast cancer will have an overall survival benefit if they get the CDK4/6 inhibitor ribociclib upfront at the time of their recurrence, even if they have not had any prior endocrine therapy at the time of presenting with metastatic disease,” study author Dr. Dennis Slamon, from the University of California Los Angeles, said in the release, adding that some experts believed to treat with endocrine therapy along first, and then if patients recur, add a CDK4/6 inhibitor.

“In other words, you get what you can out of endocrine therapy alone — and save a CDK4/6 inhibitor until the subsequent recurrence. The data from Monaleesa-3 clearly show that if postmenopausal patients receive this right up front there is a very significant benefit – not only in progression-free survival, which had already been published – but now with this new report in overall survival – which is the hardest endpoint to reach, and the most important one in terms of making an impact on the disease,” Slamon explained.

Monarch 2

In the phase 3 Monarch 2 trial, researchers randomized 669 pre/peri or postmenopausal patients with HR­-positive, HER2-negative advanced breast cancer resistant to endocrine therapy to receive either Verzenio plus Faslodex or placebo plus Faslodex.

The addition of the CDK4/6 inhibitor led to a median 9.4-month overall survival benefit compared with Faslodex with placebo. Moreover, at a median follow-up of 47.7 months, the median overall survival with the combination was 46.7 months, compared with 37.3 months in the placebo arm.

“The main take-home message from this study — and from other similar studies – is that CDK4/6 inhibitors significantly prolong the time patients remain in remission and significantly improve overall survival,” study author Dr. George Sledge, from Stanford University School of Medicine, said in the release. “Therefore, it is very reasonable to think of these as standard of care options for patients with metastatic breast cancer.”