Ribociclib plus Endocrine Therapy demonstrated improved overall survival in advanced HR+/HER2- Breast Cancer

According to findings from an exploratory analysis of the Phase-III MONALEESA-7 trial presented during the 2021 ESMO Breast Cancer Virtual Congress, “Ribociclib plus endocrine therapy demonstated improved overall survival (OS) and post-progression outcomes in pre- or postmenopausal patients with hormone receptor HR+, HER2- advanced breast cancer irrespective of age.”

In patients aged under 40 years, the median overall survival (OS) was noted as 51.3 months with ribociclib plus endocrine therapy versus 40.5 months with the placebo plus endocrine therapy, translating to a reduction of 35% in the risk of death with the CDK4/6 inhibitor. The 4-year overall survival rates were noted as 56.2% vs 34.4%, respectively.

In patients aged 40 years or older, the median overall survival was noted as 58.8 months with ribociclib plus endocrine therapy versus 51.7 months with placebo plus endocrine therapy, translating to a reduction of 19% in the risk of death with the CDK4/6 inhibitor. The 4-year overall survival rates were noted as 61.1% vs 47.8%, respectively.

According to Yen-Shen Lu, MD, PhD, a clinical associate professor in the Department of Internal Medicine at the National Taiwan University College of Medicine, and Division Chief of Medical Oncology in the Department of Oncology at the National Taiwan University Hospital in Taipei, Taiwan, during a virtual presentation of the data, “Ribociclib plus endocrine therapy prolonged overall survival and improved post-progression outcomes in pre- or perimenopausal patients with HR+, HER2- advanced breast cancer regardless of age. This effect was especially pronounced in women aged less than 40 years who typically have more aggressive disease.” 

Younger patients with HR+, HER2- advanced breast cancer typically have more aggressive disease and worse prognosis in comparison to older patients. Specifically patients aged under the 40 years have higher breast cancer mortality vs those 40 years of age or older.

Therefore, the specialists conducted an exploratory analysis to assess the effect of age on the efficacy and safety of ribociclib plus endocrine therapy vs placebo plus endocrine therapy in the trial named MONALEESA-7.

Prior outcomes from the trial MONALEESA-7 demonstrated a significant improvement in progression-free survival, overall survival, and QoL with ribociclib plus endocrine therapy vs placebo plus endocrine therapy in patients with the pre- or perimenopausal HR+, HER2- advanced breast cancer.

Although an exploratory analysis done with a median follow-up of 53.5 months showed the sustained overall survival with ribociclib plus endocrine therapy vs placebo plus endocrine therapy in the overall population. The median overall survival was noted as 58.7 months vs 48.0 months, respectively.

Shen Lu stated that, “In exploratory analysis, the baseline characteristics were normally well-balanced b/w patients aged under 40 and those who are at least 40 years of age with no notable differences between the cohorts.”

Additional findings demonstrated that PFS2, defined as the time from randomization to tumor progression on next-line treatment or death from any cause, favored ribociclib plus endocrine therapy vs placebo plus endocrine therapy in patients aged under the age of 40 and those who are 40 years of age or older.

In the former population, the median PFS2 was noted as 46.0 months with ribociclib plus endocrine therapy versus 25.5 months with placebo plus endocrine therapy. In the latter population, the median PFS2 was noted as 43.6 months with ribociclib plus endocrine therapy versus 32.7 months with placebo plus endocrine therapy.

Furthermore, the time to first chemotherapy was delayed with ribociclib plus endocrine therapy versus placebo plus endocrine therapy across the both age subgroups. In patients aged under 40 years, the median time to first chemotherapy was not evaluable with the ribociclib plus endocrine therapy versus 36.6 months with placebo plus endocrine therapy. In patients aged 40 years or older, the median time to first chemotherapy was noted as 50.2 months versus 36.8 months, respectively.

The combination of ribociclib and endocrine therapy also prolonged chemo free survival in both the age subgroups. In patients under the age of 40 year, the median chemo free survival was noted as 46.5 months with ribociclib plus endocrine therapy versus 22.7 months with placebo plus endocrine therapy. In patients aged 40 years or older, the median chemo free survival was noted as 41.5 months versus 27.6 months, respectively.

Regarding treatment interruption in patients aged under 40 years, 76.5% interrupted treatment in the ribociclib plus endocrine therapy arm versus 90.9% in the placebo plus endocrine therapy arm. In patients aged 40 years or older, 79.7% versus 90.8% interrupted treatment in the ribociclib plus endocrine therapy and placebo plus endocrine therapy arms, respectively.

The subsequent antineoplastic treatment in patients aged under 40 years was received by 77.3% of patients in the arm of ribociclib plus endocrine therapy versus 75.0% of patients in the arm of placebo plus endocrine therapy. In patients aged 40 years or older, 77.2% versus 79.2% received subsequent antineoplastic treatment in the ribociclib plus endocrine therapy and placebo plus endocrine therapy arms, respectively.

Among patients aged under 40, subsequent CDK4/6 inhibition at any point following study interruption was received by 16.0% versus 27.5% in the ribociclib plus endocrine therapy and placebo plus endocrine therapy arms, respectively. Among patients aged 40 years or older, the subsequent CDK4/6 inhibition was received by 11.6% versus 25.7% of patients in the ribociclib tablet plus endocrine therapy and placebo plus endocrine therapy arms, respectively.

According to Lu, “In patients who interrupted the treatment, subsequent antineoplastic therapy use, including CDK4/6 inhibitors, was comparable in both the age subgroups.”

“Despite a higher proportion of patients in the placebo arm receiving subsequent CDK4/6 inhibition, the overall survival  benefit of ribociclib was evident in the both age subgroups,” Lu added. 

Adverse effects noted as consistent with those reported in the overall group. Discontinuation of treatment due to adverse effects with ribociclib plus endocrine therapy and placebo plus endocrine therapy, respectively, occurred in 5.1% versus 3.4% of patients aged under 40 years and 4.6% versus 3.6% of patients aged 40 years or older.

Concluded by Lu, “The safety results were identical in the both groups in comparison to those of the overall population, and there were no notable safety differences between the age subgroups.”

Reference:

https://www.novartis.com/news/media-releases/novartis-kisqali-reports-longest-median-overall-survival-postmenopausal-hrher2-metastatic-breast-cancer-patients

Related:

What is Ribociclib?

Ribociclib was initially approved by the US FDA in the month of March 2017 and by the European Commission (EC) in the month of August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer along with an aromatase inhibitor based on findings from the pivotal trial MONALEESA-2.

The ribociclib 200 mg together with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine-based therapy, and also indicated for use along with fulvestrant as both first- or second-line therapy in the postmenopausal women by the FDA in the month of July, 2018 and by the EC in the month of December, 2018. 

Ribociclib was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.