Novel Combination Shows Potential as First-Line Breast Cancer Treatment

Findings from the phase 3 trial MONALEESA-2 suggest that LEE011 (ribociclib) plus letrozole may be a beneficial first-line treatment for postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.

LEE011 is a selective cyclin dependent kinase inhibitor, which works by inhibiting cyclin dependent kinase 4 and 6 (CDK4/6). When overexpressed, these proteins can cause cancer cells to grow and divide uncontrollably. Included in the study were 668 patients stratified by the presence of liver and/or lung metastases, according to a press release from Novartis.

Patients were randomized to receive LEE011 600 mg/daily or placebo in combination with 2.5 mg of letrozole per day. Investigators found that LEE011 with letrozole offered significantly longer progression-free survival compared with treatment with letrozole monotherapy, which was the primary endpoint, according to Novartis.

Secondary endpoints included overall survival, overall response rate, clinical benefit rate, health-related quality of life, safety, and tolerability. They also discovered that the experimental drug was able to reduce the risk of death or progression over 44% compared with letrozole.

Novartis said these findings were seen across all subgroups. A majority of women treated with LEE011 plus letrozole had tumor shrinkage of over 30%.

Due to the extension of progression-free survival and overall benefit of LEE011, the trial was stopped early. A follow-up measure of overall survival is ongoing, Novartis wrote.

“The MONALEESA-2 results show the combination of LEE011 plus letrozole represents a significant step forward in the management of HR+ metastatic breast cancer and, if approved, would be a major addition to the treatment options these patients have,” said principal investigator Gabriel N. Hortobagyi, MD. “Women living with metastatic breast cancer will be on treatment for the rest of their lives, so it is critical to find treatment options that effectively delay progression.”

Most of the adverse events reported were mild to moderate, and typically identified early in treatment, according to Novartis. These events were mostly managed through dose interruption and reduction.

The most common events were neutropenia, nausea, infection, fatigue, and diarrhea. Investigators found that the discontinuation due to adverse events was more common among patients taking LEE011 plus letrozole (7.5%), compared with those taking letrozole monotherapy (2.1%).

This is the only phase 3 trial of a CDK4/6 inhibitor being investigated as a first-line treatment that was stopped early due to significant progression free survival, according to Novartis. LEEO11 is currently not approved in any market.

“We are excited about these strong results that show LEE011 has the potential to be an effective first-line treatment option that could improve outcomes for women with HR+/HER2- advanced breast cancer,” said Bruno Strigini, CEO, Novartis Oncology. “Following the Breakthrough Therapy designation granted by the FDA in August of this year, we look forward to working closely with health authorities to bring a much needed new treatment option to these patients as quickly as possible.”