Kisqali-Faslodex Combo Prolongs Survival of Postmenopausal Women with Advanced Breast Cancer, Phase 3 Trial Shows

Kisqali (ribociclib) in combination with Faslodex (fulvestrant) prolongs the survival of postmenopausal women with HR-positive, HER2-negative, advanced or metastatic breast cancer, interim analysis of a Phase 3 clinical trial shows.

The findings were presented in a late-breaking presentation titled, “Overall survival (OS) results of the phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR ), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) treated with fulvestrant (FUL) ribociclib (rib),” at the European Society for Medical Oncology (ESMO) 2019 Congress, held Sept. 27–Oct. 1, in Barcelona, Spain.

Kisqali is a targeted therapy marketed by Novartis. It works by interfering with the activity of cyclin-dependent kinases (CDK) 4/6, which are enzymes that regulate cell proliferation and growth, and often are overactive in breast cancer. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of women with HR-positive, HER2-negative metastatic breast cancer.

Faslodex is a type of hormone therapy marketed by AstraZeneca. It was first approved by the FDA in 2002 to treat postmenopausal women whose disease progressed after being treated with anti-estrogen therapy (e.g., tamoxifen) and later for other types of breast cancer.

The effects of Kisqali in combination with Faslodex as a first- or second-line therapy are currently being assessed in the randomized, double-blind, placebo-controlled, MONALEESA-3 Phase 3 trial (NCT02422615).

The trial enrolled 726 postmenopausal women with HR-positive, HER2-negative, advanced or metastatic breast cancer who were assigned randomly to either the Kisqali-Faslodex combo, or a placebo in combination with Faslodex.

The trial’s primary goal was to determine the time patients lived until disease progression or death due to any cause (progression-free survival, or PFS). Secondary outcomes included overall survival, the percentage of patients who responded to treatment, and the duration of response.

In a prior analysis of MONALEESA-3, which supported Kisqali’s approval in combination with an aromatase inhibitor for the first-line treatment of HR-positive, HER2-negative advanced or metastatic breast cancer, researchers already had shown that the combination reduced the risk of disease progression or death by 42%, meeting the trial’s primary goal.

New findings from a pre-planned interim analysis presented at the ESMO Congress now showed the trial met its secondary goal of overall survival, with Kisqali reducing the risk of death by 28% in the overall patient population.

These survival benefits were seen in all patient sub-groups, including among women who received the Kisqali-Faslodex combo as their initial therapy (median survival not reached vs. 45.1 months), or second-line treatment (40.2 months vs. 32.5 months), compared to those treated with Faslodex alone.

Updated progression-free survival results also showed that, when administered as a first-line therapy, the Kisqali-Faslodex combo also increased the median time women lived without disease progression or death from 19.2 to 33.6 months.

Findings also showed that Kisqali delayed the time at which women had to start chemotherapy, as well as the time to disease progression on a subsequent therapy.

The therapy’s safety profile was consistent with previous data from MONALEESA-3. The most common severe (grade 3) and life-threatening (grade 4) reported during the study included low white blood cell counts (neutropenia), liver toxicity, respiratory disorders, and interstitial lung disease (ILD).

MONALEESA-3 is the second Phase 3 trial — after MONALEESA-7 (NCT02278120) — in which a Kisqali-based combo therapy met the secondary overall survival goal in women with advanced forms of breast cancer at a pre-planned interim analysis.

“The remarkable results from MONALEESA-3 and MONALEESA-7 make Kisqali the CDK4/6 inhibitor with consistently superior overall survival,” Susanne Schaffert, PhD, president of Novartis Oncology, said in a press release. “In nearly 25 years, the five-year survival rates in HR metastatic breast cancer have improved by less than 5%. We are committed to helping give these women more life and are reimagining a world where metastatic breast cancer becomes a curable disease.”

Dennis J. Slamon, MD, director of Clinical/Translational Research at the University of California, presented the findings of MONALEESA-3 at the ESMO Congress. “Seen now in two Phase 3 trials, ribociclib consistently and significantly prolongs life among premenopausal and postmenopausal women, and in combination with an aromatase inhibitor and fulvestrant. These results arm oncologists with more evidence to make a confident treatment choice for their hormone receptor-positive metastatic breast cancer patients,” Slamon said.

MONALEESA-3 was not the only trial in which a combination therapy of a CDK4/6 inhibitor with Faslodex was found to increase the survival of women with advanced forms of breast cancer.

New data from MONARCH 2 (NCT02107703), also presented during the ESMO Congress, showed that Verzenio (abemaciclib) — a CDK4/6 inhibitor marketed by Eli Lilly — in combination with Faslodex increased the median time women lived from 37.3 to 46.7 months, reducing the risk of death by 24% in the overall patient population. These survival benefits also were seen on all patient sub-groups, including among women who had poor prognoses.

Like the Kisqali-Faslodex combo in MONALEESA-3, the Verzenio-Faslodex combo in MONARCH 2 also delayed the time at which women had to start chemotherapy and the time to disease progression on a subsequent therapy.

“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. Therefore it is very reasonable to think of these as standard of care options for patients with metastatic breast cancer,” George Sledge, MD, said in a press release. Sledge, a professor of oncology at Stanford University School of Medicine, presented the findings of MONARCH 2 at the ESMO Congress, .

“The results of MONARCH 2 nicely complement those reported in MONALEESA-3,” said Nadia Harbeck, MD, PhD, head of the Breast Cancer Center at the University of Munich in Germany.

“Abemaciclib is the third CDK4/6 inhibitor to show an overall survival benefit in advanced HR HER2- 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,” Harbeck said.