Ribociclib/Endocrine Therapy Improves OS Regardless of Age in Advanced HR+/HER2- Breast Cancer

Ribociclib (Kisqali) plus endocrine therapy improved overall survival (OS) and post-progression outcomes in pre- or postmenopausal patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer irrespective of age, according to findings from an exploratory analysis of the phase 3 MONALEESA-7 trial (NCT02278120) presented during the 2021 ESMO Breast Cancer Virtual Congress.

In patients under the age of 40, the median OS was 51.3 months with ribociclib/endocrine therapy vs 40.5 months with placebo/endocrine therapy, translating to a 35% reduction in the risk of death with the CDK4/6 inhibitor (HR, 0.651; 95% CI, 0.431-0.983). The 4-year OS rates were 56.2% vs 34.4%, respectively.

In patients aged 40 or above, the median OS was 58.8 months with ribociclib/endocrine therapy vs 51.7 months with placebo/endocrine therapy, translating to a 19% reduction in the risk of death with the CDK4/6 inhibitor (HR, 0.810; 95% CI, 0.617-1.065). The 4-year OS rates were 61.1% vs 47.8%, respectively.

“Ribociclib plus endocrine therapy prolonged OS and improved post-progression outcomes in pre- or perimenopausal patients with HR-positive, HER2-negative advanced breast cancer regardless of age. This effect was especially pronounced in women less than 40 [years of age] who typically experience more aggressive disease,” 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, said in a virtual presentation of the data.

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

Therefore, investigators conducted an exploratory analysis to evaluate the effect of age on the efficacy and safety or ribociclib/endocrine therapy vs placebo/endocrine therapy in the MONALEESA-7 trial.

Prior results from the MONALEESA-7 trial showed a significant improvement in progression-free survival (PFS), OS, and quality of life with the combination of ribociclib and endocrine therapy vs placebo plus endocrine therapy in patients with pre- or perimenopausal HR-positive, HER2-negative advanced breast cancer.

Moreover, an exploratory analysis performed with a median follow-up of 53.5 months demonstrated sustained OS with ribociclib/endocrine therapy vs placebo/endocrine therapy in the overall population. The median OS was 58.7 months vs 48.0 months, respectively (HR, 0.76; 95% CI, 0.61-0.96).

In the exploratory analysis, baseline characteristics were generally well-balanced between patients under the age of 40 and those at least 40 years of age with no notable differences between the cohorts, said Shen Lu.

Additional findings indicated that PFS2, defined as the time from randomization to tumor progression on next-line treatment or death from any cause, favored ribociclib/endocrine therapy vs placebo/endocrine therapy in patients under the age of 40 and those 40 years of age or older. In the former group, the median PFS2 was 46.0 months with ribociclib/endocrine therapy vs 25.5 months with placebo/endocrine therapy (HR, 0.588; 95% CI, 0.401-0.862). In the latter group, the median PFS2 was 43.6 months with ribociclib/endocrine therapy vs 32.7 months with placebo/endocrine therapy (HR, 0.705; 95% CI, 0.555-0.894).

Furthermore, the time to first chemotherapy was delayed with ribociclib/endocrine therapy vs placebo/endocrine therapy across both age subgroups. In patients under the age of 40, the median time to first chemotherapy was not evaluable with ribociclib/endocrine therapy vs 36.6 months with placebo/endocrine therapy (HR, 0.649; 95% CI, 0.416-1.011). In patients 40 years of age or older, the median time to first chemotherapy was 50.2 months vs 36.8 months, respectively (HR, 0.693; 95% CI, 0.534-0.898).

The addition of ribociclib to endocrine therapy also prolonged chemotherapy-free survival in both age subgroups. In patients under the age of 40, the median chemotherapy-free survival was 46.5 months with ribociclib/endocrine therapy vs 22.7 months with placebo/endocrine therapy (HR, 0.582; 95% CI, 0.398-0.851). In patients 40 years of age or older, the median chemotherapy-free survival was 41.5 months vs 27.6 months, respectively (HR, 0.679; 95% CI, 0.541-0.852).

Regarding treatment discontinuation in patients under the age of 40, 76.5% discontinued treatment in the ribociclib/endocrine therapy arm vs 90.9% in the placebo/endocrine therapy arm. In patients 40 years of age or older, 79.7% vs 90.8% discontinued treatment in the ribociclib/endocrine therapy and placebo/endocrine therapy arms, respectively.

Subsequent antineoplastic treatment in patients under the age of 40 was received by 77.3% of patients in the ribociclib/endocrine therapy arm vs 75.0% of patients in the placebo/endocrine therapy arm. In patients 40 years of age or older, 77.2% vs 79.2% received subsequent antineoplastic treatment in the ribociclib/endocrine therapy and placebo/endocrine therapy arms, respectively.

Among patients under the age of 40, subsequent CDK4/6 inhibition at any point after study discontinuation was received by 16.0% vs 27.5% in the ribociclib/endocrine therapy and placebo/endocrine therapy arms, respectively. Among patients 40 years of age or older, subsequent CDK4/6 inhibition was received by 11.6% vs 25.7% of patients in the ribociclib/endocrine therapy and placebo/endocrine therapy arms, respectively.

“In patients who discontinued treatment, subsequent antineoplastic therapy use, including CDK4/6 inhibitors was comparable in both age subgroups,” said Lu. “Despite a higher proportion of patients in the placebo arm receiving subsequent CDK4/6 inhibition, the OS benefit of ribociclib was evident in both age subgroups.”

Adverse effects (AEs) were consistent with those reported in the overall population. Treatment discontinuations due to AEs with ribociclib/endocrine therapy and placebo/endocrine therapy, respectively, occurred in 5.1% vs 3.4% of patients under the age of 40 and 4.6% vs 3.6% of patients 40 years of age or older.

“The safety findings were similar in both groups compared with those of the overall population, and there were no notable safety differences between the age subgroups,” concluded Lu.

Reference

Lu YS, El-Saghir N, Hurvitz S, et al. Overall survival results by age subgroup from the phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2- advanced breast cancer treated with endocrine therapy ±ribociclib. Presented at: 2021 ESMO Breast Cancer Virtual Congress; May 5-8, 2021. Abstract 93MO.