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

Verzenio (abemaciclib) in combination with Faslodex (fulvestrant) prolongs the survival of women with HR-positive, HER2-negative, advanced or metastatic breast cancer who had been treated previously with endocrine therapy, a Phase 3 clinical trial shows.

The findings were presented in a late-breaking presentation, “MONARCH 2: Overall survival of abemaciclib plus fulvestrant in patients with HR , HER2- advanced breast cancer,” at the European Society for Medical Oncology (ESMO) 2019 Congress, held Sept. 27–Oct. 1 in Barcelona, Spain, and  published simultaneously in JAMA Oncology.

Verzenio is a cancer medication marketed by Eli Lilly. It is a strong inhibitor of cyclin-dependent kinases (CDK)4/6, which are enzymes that regulate cell proliferation and growth, and often are overactive in breast cancer. It was approved by the U.S. Food and Drug Administration (FDA) in 2017 for the treatment of certain types of advanced or metastatic breast cancers.

Faslodex is a type of hormone therapy marketed by AstraZeneca. It was 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 Verzenio in combination with Faslodex are currently being assessed in the randomized, double-blind, placebo-controlled, MONARCH 2 Phase 3 trial (NCT02107703).

The trial enrolled 669 pre-, peri-, and postmenopausal women with HR-positive, HER2-negative metastatic breast cancer whose disease progressed following endocrine therapy.

All patients were randomly assigned to receive either the Verzenio-Faslodex combo, or a placebo in combination with Faslodex, until disease progression or unacceptable toxicity.

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 goals included overall survival, the percentage of patients who responded to treatment, and the duration of response.

Previous findings from MONARCH 2 demonstrated the study met its primary goal, as patients treated with the Verzenio-Faslodex combo lived longer without signs of disease progression (16.4 months) compared to those treated with a placebo (9.3 months).

A pre-planned interim analysis of MONARCH 2 also demonstrated that patients treated with Verzenio lived longer than those treated with Faslodex alone, meaning that one of the key secondary goals of MONARCH 2 also had been achieved.

Eli Lilly now presented updated data from the trial. At the time of data cut-off (June 20), 338 of the 669 women enrolled initially had died, but Verzenio increased the median time women lived from 37.3 to 46.7 months, reducing the risk of death by 24%.

These survival benefits were seen in all patient sub-groups, including among women who had a poor prognosis, (i.e., those whose cancer had returned quickly following endocrine therapy, or had spread to other organs).

An exploratory analysis also showed that Verzenio delayed the time at which women had to start chemotherapy from 22.1 to 50.2 months, and delayed the time to disease progression on a subsequent therapy (23.1 months vs. 20.6 months).

The therapy’s safety profile was consistent with previous data from MONARCH 2; no new safety concerns have been reported with longer patient follow-up (median of 47.7 months).

“Hearing that the results of MONARCH 2 showed significant improvement in overall survival for women living with HR , HER2- advanced breast cancer is exciting and welcomed. Women with this type of breast cancer now have a treatment option that may allow them more time to achieve their dreams,” Shirley Mertz, president of the Metastatic Breast Cancer Network, said in a press release.

“It has been a major challenge in our field to extend survival, our ultimate goal, with current therapies for HR , HER2- advanced breast cancer,” said Maura Dickler, MD, vice president of late stage development at Lilly Oncology.

“We are excited that Verzenio in combination with fulvestrant has demonstrated the ability to improve overall survival. These are clinically meaningful results that confirm Verzenio can keep advanced breast cancer from progressing and can extend life. Until there is a cure, we will be persistent in exploring how we can help more people live longer with advanced breast cancer,” she said.

Lilly will continue to monitor the remaining patients in the trial (17% of those originally assigned to Verzenio and 4% of those assigned originally to a placebo) and is already planning future post-hoc analyses. The company also is planning to submit these findings to regulatory health authorities worldwide.

In addition to new data from MONARCH 2, the company also presented promising findings from MONARCHplus (NCT02763566), the first Phase 3 trial assessing the effects of Verzenio in women with HR-positive, HER2-negative advanced breast cancer, and monarcHER (NCT02675231), the first Phase 3 trial assessing the effects of Verzenio in combination with endocrine therapy in women with HR-positive, HER2-positive breast cancer, at the ESMO Congress.