OS Improves With Addition of Ribociclib/Endocrine Therapy in Advanced Breast Cancer

Regardless of age the combination of ribociclib (Kisqali) and endocrine therapy led to improved overall survival (OS) in pre- or postmenopausal patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer. The results of an exploratory analysis from the phase 3 MONALEESA-7 trial (NCT02278120) were presented during the 2021 European Society for Medical Oncology (ESMO) Breast Cancer Virtual Congress.¹

In patients under 40 years, 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 older, the median OS was 58.8 months with ribociclib/endocrine therapy vs 51.7 months with placebo/endocrine therapy. This translated 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 postprogression 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 old], who typically experience more aggressive disease,” said Yen-Shen Lu, MD, PhD, a clinical associate professor in the Department of Internal Medicine at National Taiwan University College of Medicine, and division chief of medical oncology in the Department of Oncology at National Taiwan University Hospital in Taipei, Taiwan, in a virtual presentation of the data.

Patients under 40 years of age with HR-positive, HER2-negative advanced breast cancer typically have more aggressive disease and a worse prognosis compared with older patients.

Specifically, patients under 40 years have a higher breast cancer mortality rate vs those aged 40 or older. Therefore, investigators conducted an exploratory analysis to evaluate the effect of age on the efficacy and safety of ribociclib/endocrine therapy vs placebo/endocrine therapy in the MONALEESA-7 trial.

Prior results from the 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 40 years and those aged at least 40 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 40 years and those aged 40 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 40 years, 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 aged 40 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 aged 40 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).

In patients under 40 years, 76.5% discontinued treatment in the ribociclib/endocrine therapy arm vs 90.9% in the placebo/endocrine therapy arm. In those aged 40 or older, 79.7% vs 90.8% discontinued treatment in the ribociclib/endocrine therapy and placebo/endocrine therapy arms, respectively (TABLE).

Subsequent antineoplastic treatment in those under 40 years 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 aged 40 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, sub-sequent 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, respe-tively. Among those aged 40 or older, 11.6% vs 25.7% of patients in the ribociclib/endocrine therapy and placebo/endocrine therapy arms, respectively, received subsequent CDK4/6 inhibition.

“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 events (AEs) were consistent with those reported in the overall population. Treatment discontinuation due to AEs with ribociclib/endocrine therapy and placebo/endocrine therapy, respectively, occurred in 5.1% vs 3.4% of patients under 40 years and in 4.6% vs 3.6% of those aged 40 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

_{1. 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. Ann Oncol. 2021;32(suppl 2):S60-S78. doi:10.1016/annonc/annonc508}