Novartis’s Monaleesa study show PFS in breast cancer treatment

Novartis has announced  additional analyses from the Phase III MONALEESA-2 study that show LEE011 (ribociclib) plus letrozole significantly prolonged progression-free survival (PFS).

PES was visible across pre-planned patient subgroups with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer, including post-menopausal women diagnosed de novo, those with visceral liver and lung metastases, and those with bone-only disease.

These findings demonstrate the strength of LEE011 plus letrozole in the first-line setting, showing that treatment benefit was evident across all patient subgroups regardless of their disease burden or tumor location, including those patients with aggressive breast cancer.

“Results from the de novo subgroup of women in the MONALEESA-2 trial establish ribociclib in combination with letrozole as a meaningful treatment option in the first-line setting for this patient population,” said Joyce O’Shaughnessy, MD, Co-Chair, Breast Cancer Research, Texas Oncology-Baylor Charles A. Sammons Cancer Center. “These de novo patients are often diagnosed initially with advanced breast cancer that has already metastasized, so it is critical to start them with treatments that extend time until disease progression.”

“Breast cancer that has metastasized to areas such as the liver or lungs can often be more challenging to effectively treat with current standards of care,” said Howard A. Burris, MD, President, Clinical Operations and Chief Medical Officer, Sarah Cannon. “We have been encouraged by the MONALEESA-2 results because treatment benefit was observed regardless of the number of metastatic sites and was maintained across all subgroups taking ribociclib plus letrozole. Our observations indicate that this novel therapy may be a promising treatment option for many patients living with advanced forms of breast cancer.”

First-line ribociclib + letrozole in patients with de novo HR+, HER2- advanced breast cancer: A subgroup analysis of the MONALEESA-2 trial

A predefined subgroup analysis of the MONALEESA-2 trial evaluated the safety and efficacy of LEE011 plus letrozole versus letrozole alone in 227 patients with de novo advanced breast cancer, defined as disease found to be metastatic at the time of first diagnosis. Because de novo disease has not been previously treated with systemic treatment for early-stage breast cancer, tumors may exhibit a different disease biology, which could result in varied responses compared to patients who experienced recurrence. In patients with de novo advanced breast cancer, LEE011 plus letrozole reduced the risk of disease progression or death by 55% over letrozole alone (HR=0.448 [95% CI: 0.267-0.750])[1]. The 12-month PFS rate was 82% in the LEE011 plus letrozole arm compared to 66% with letrozole alone, said Novartis in its press release.

Consistent with the overall study population, most adverse events were mild to moderate in severity, identified early through routine monitoring, and generally managed through dose interruption and reduction. The most common grade 3/4 adverse events (>=15% of patients with de novo advanced breast cancer; LEE011 plus letrozole vs. letrozole alone) were neutropenia (55.3% vs. 0.9%) and leukopenia (21.1% vs. 0%).

First-line ribociclib + letrozole in patients with HR+, HER2- advanced breast cancer presenting with visceral metastases or bone-only disease: A subgroup analysis of the MONALEESA-2 trial

In separate predefined subgroups, 393 patients with advanced breast cancer with visceral metastases and 147 patients with bone-only disease were evaluated as part of the MONALEESA-2 trial. Those with visceral metastases have metastatic growth at the site of the lung or liver, and typically have a poorer prognosis than patients with non-visceral disease. Results of these analyses show that first-line LEE011 plus letrozole was well tolerated and reduced the risk of disease progression or death by 47% (patients with visceral disease: HR=0.535 [95% CI: 0.385-0.742]) and by 31% (patients with bone-only disease: HR=0.690 [95% CI: 0.381-1.249]) respectively. Treatment benefit with LEE011 in combination with letrozole was observed regardless of the number of metastatic sites and (HR=0.607 (95% CI: 0.437-0.845) among patients with less than 3 metastases; HR=0.456 (95% CI: 0.298-0.700) among patients with 3 or more metastases), explained Novartis.

Among patients with visceral metastases the most frequent grade 3/4 adverse events (>=20% of patients; LEE011 plus letrozole vs. letrozole alone) were neutropenia (64.0% vs 1%) and leukopenia (20.8% vs 0.5%). Among patients with bone-only disease the most frequent grade 3/4 adverse events (>=20% of patients; LEE011 plus letrozole vs. letrozole alone) were neutropenia (53.6% vs 1.3%) and leukopenia (23.2% vs 1.3%).

“These additional results from the MONALEESA-2 study are very promising for women with HR+ advanced breast cancer,” said Bruno Strigini, CEO, Novartis Oncology. “We believe LEE011 could significantly benefit a broad range of women as an initial treatment for metastatic breast cancer and look forward to working with global health authorities to bring this new treatment to patients.”

The MONALEESA-2 study is ongoing to evaluate secondary endpoints, including overall survival. LEE011 received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) in August 2016 and Priority Review in October 2016.

About Advanced Breast Cancer

Up to one-third of patients with early-stage breast cancer will subsequently develop metastatic disease. Metastatic breast cancer is the most serious form of the disease and occurs when the cancer has spread to other parts of the body, such as the brain, bones or liver. Advanced breast cancer comprises metastatic breast cancer (stage 4) and locally advanced breast cancer (stage 3). Survival rates for women living with advanced breast cancer are lower than those for women with earlier stage disease. The 5-year relative survival rate for stage 3 breast cancer is approximately 72%, while metastatic (stage 4) breast cancer has a 5-year relative survival rate of approximately 22%.