Verzenio-Faslodex Combo Prolongs Survival in Advanced Breast Cancer, Interim Phase 3 Data Show

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 previously treated with endocrine therapy, interim analysis of a Phase 3 trial shows.

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 are often overactive in breast cancer.

In 2017, Verzenio was approved by the U.S. Food and Drug Administration (FDA) for the treatment of certain types of advanced or metastatic breast cancers.

Faslodex is a form of hormone therapy marketed by AstraZeneca. It was approved by the FDA in 2002 for the treatment of 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. Treatment lasted until disease progression or unacceptable toxicity.

The trial’s primary endpoint was to determine patients’ progression-free survival (the time patients live without their disease worsening). Secondary endpoints included assessing patients’ overall survival, objective response, and duration of response to treatment.

Previous findings from MONARCH 2 demonstrated the study’s primary outcome was reached, with patients treated with the active combination having a significant improvement in progression-free survival (16.4 months) compared to those treated with a placebo (9.3 months).

In addition to the 45% reduction in the risk of disease progression or death, a key secondary endpoint was also met, with responses to Verzenio-Faslodex more than doubling those on the control arm — 48.1% versus 21.3%. These findings were the foundation for the approval of the Verzenio-Faslodex combo in more than 50 countries.

Now, data from a pre-planned interim analysis of the trial showed that patients treated with the combo therapy also lived longer than those on a placebo, meaning that one of the key secondary endpoints of MONARCH 2 has also been met. No new safety issues have been reported in the interim analysis.

“I believe we must continue to fight this devastating disease because the women who are living with metastatic breast cancer want to do everything they can to lead more fulfilling lives and be there for those who need them most,” Anne White, president of Lilly Oncology, said in a press release.

“While Verzenio had already shown an impressive benefit for progression-free survival, we are delighted that Verzenio is the first and only CDK4/6 inhibitor in combination with fulvestrant that has significantly extended life for both pre/peri- and postmenopausal women.”

Eli Lilly is planning to submit applications to regulatory health authorities worldwide, and present the complete data of MONARCH 2 at a medical meeting later this year.

“This definitive overall survival analysis from MONARCH 2 showed significant improvement in overall survival for women living with HR , HER2- metastatic breast cancer, a complex disease that remains incurable,” said Maura Dickler, MD, vice president of late stage development of Lilly Oncology.

“For many doctors and patients, overall survival is the most important endpoint. It’s been difficult in the past to achieve meaningful improvements in this endpoint for women with advanced breast cancer, including those whose cancer progressed after prior endocrine therapy,” she said.