Novartis announced the updated findings from the phase III Monaleesa-2 study that reinforce the efficacy and safety of Kisqali (ribociclib) plus letrozole in postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. After an additional 11 months of follow-up, a median progression-free survival (PFS) of 25.3 months (95% CI: 23.0-30.3) for Kisqali plus letrozole and 16.0 months (95% CI: 13.4-18.2) for letrozole alone was observed (HR=0.568 (95% CI: 0.457-0.704; p<0.0001)). These data will be presented on Sunday, June 4, 2017 at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

These updated results further support that Kisqali plus letrozole improves PFS as a first-line treatment across all patient subgroups. After two years of treatment, the progression-free survival rate was 54.7% in the Kisqali plus letrozole arm compared to 35.9% in patients treated with letrozole alone. In a cohort of 213 US patients treated as part of Monaleesa-2, the median PFS was 27.6 months with Kisqali plus letrozole and 15.0 months with letrozole alone (HR=0.527 (95% CI: 0.351-0.793)).

Treatment benefit remained consistent across all patient subgroups regardless of demographics or disease characteristics, including women with visceral disease and those diagnosed de novo. In women with measurable disease at baseline, 55% saw their tumor size shrink by at least 30% (overall response rate (ORR)) compared to 39% with letrozole plus placebo. Follow-up to measure overall survival is ongoing as data remain immature.

"This new look at the Monaleesa-2 data, after an additional year of follow-up, demonstrates the continued efficacy of ribociclib plus letrozole," said Gabriel N. Hortobagyi, MD, Professor of Medicine, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center and Monaleesa-2 Principal Investigator. "With more than two years of follow-up, the PFS data confirm the inclusion of ribociclib plus an aromatase inhibitor as a strong option among first-line treatments for HR-positive, HER2-negative advanced breast cancer."

A separate analysis of patient-reported, health-related quality of life (HRQoL) outcomes from the Monaleesa-2 trial presented at ASCO (Abstract #1020) showed no significant difference in quality of life for women taking Kisqali plus letrozole compared to those taking letrozole alone. This suggests that adverse events did not significantly impact HRQoL.

Updated safety data from the Monaleesa-2 trial show the safety profile of Kisqali plus letrozole remained consistent and the incidence of laboratory and electrocardiogram (ECG) irregularities is similar to that observed at the first interim analysis. At the time of this updated analysis, the most common (>=10%) grade 3/4 laboratory abnormalities were as follows for Kisqali plus letrozole compared to letrozole alone: decreased neutrophils (62.6% vs 1.5%), decreased leukocytes (36.8% vs 1.5%), decreased lymphocytes (16.2% vs 3.9%) and elevated alanine aminotransferase (11.4% vs 1.2%).

"Updated Monaleesa-2 results validate the sustained efficacy and established safety profile of Kisqali plus letrozole in patients with HR+/HER2- metastatic breast cancer and confirm the data that supported its recent FDA approval," said Vas Narasimhan, MD, head, Global Drug Development and Chief Medical Officer, Novartis. "We are excited about the potential of Kisqali, and are continuing to evaluate its activity in several Phase III trials with multiple hormonal therapy combinations across a broad range of patient populations, including in the adjuvant setting. We look forward to sharing new results with the scientific community in the coming months and years."

The Monaleesa clinical trial program includes two additional Phase III trials in advanced breast cancer, Monaleesa-3 and Monaleesa-7, which are evaluating the efficacy and safety of Kisqali in combination with other endocrine partners. Novartis also is enrolling patients in a study to further evaluate Kisqali in men and pre- or postmenopausal women (CompLEEment-1) and initiating Phase III trials evaluating Kisqali in the adjuvant therapy setting (EarLEE-1 and EarLEE-2).

Kisqali was approved by the US Food and Drug Administration (FDA) on March 13, 2017, as a first-line treatment for HR+/HER2- metastatic breast cancer in combination with any aromatase inhibitor.