Kisqali Plus Endocrine Therapy Improves Survival in HR+/HER2– Breast Cancer

Patients with hormone receptor (HR)–positive HER2-negative advanced breast cancer who were treated with Kisqali (ribociclib) plus endocrine therapy obtained consistent survival benefits compared with placebo plus endocrine therapy, recent study findings demonstrated.

The survival benefit was present regardless of the patient’s age, according to findings from an analysis of the MONALEESA trials presented at the 2023 San Antonio Breast Cancer Symposium (SABCS).

Investigators reported a median progression-free survival (the time during and after treatment when a patient with cancer lives with the disease without worsening) of 31.8 months with the Kisqali combination versus 16.4 months with placebo plus endocrine therapy in patients younger than 65 years. Additionally, the median progression-free survival in each respective arm was 35.7 months versus 19.2 months in patients 65 years and older but younger than 75 and 31.1 months versus 19.2 months in those 75 years or older.

Among patients younger than 65 years, the median overall survival (the time after the start of treatment when a patient with cancer is still alive) was 67.6 months in the Kisqali arm versus 51.7 months in the placebo arm. The median overall survival in each respective arm was 72.6 months versus 59.8 months in patients 65 years and older but younger than 75 and 62.1 months versus 52.8 months in those 75 years and older.

The median time to next chemotherapy in patients younger than 65 years was 58 months in the Kisqali arm compared with 40.2 months in the placebo arm. Additionally, the median time to next chemotherapy in each respective arm was not evaluable (meaning more than half of the patients still did not undergo chemotherapy when researchers assessed this outcome), 48.3 months in patients 65 years and older but younger than 75 and 80.3 months versus 42.3 months in patients 75 years and older.

“Analysis showed that (Kisqali plus endocrine therapy) is an effective and well-tolerated treatment in general,” presenting author Dr. Lowell Hart, a medical oncologist and hematologist at Florida Cancer Specialists Sarah Cannon Research Institute in Fort Myers, and Wake Forest University School of Medicine in Winston-Salem, North Carolina, said. “We didn’t see any usual (side) effects in the more elderly patients.”

Investigators evaluated outcomes among patients who are postmenopausal in the phase 3 MONALEESA-2 trial and phase 3 MONALEESA-3 trial, as well as patients who were premenopausal in the phase 3 MONALEESA-7 trial. The median follow-up for the MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials, respectively, was 79.8 months, 70.8 months, and 54.4 months.

In the MONALEESA-2 trial, 668 patients were randomly assigned to receive Kisqali once a day or a matched placebo followed by Femara (letrozole). In the MONALEESA-3 trial, 726 patients were randomly assigned to receive Kisqali or a matched placebo followed by fulvestrant. The MONALEESA-7 trial included 672 patients who were randomly assigned to receive Kisqali or placebo followed by tamoxifen or a nonsteroidal aromatase inhibitor plus goserelin.

Investigators of this analysis assessed progression-free survival, overall survival and time to next chemotherapy across patient age groups. The analysis also evaluated patient-reported outcomes. Additionally, investigators assessed the time to definitive deterioration in global health status and change in physical functioning.

The overall population in the dataset included 1,229 patients. Of these patients, 773 were younger than 75 years and 456 were older than 65 years. Investigators reported that characteristics at the start of the study were comparable across age groups in each treatment arm, although they noted a few key differences. In the Kisqali and placebo arms, respectively, there was a higher proportion of patients in the 75 years and older group with an ECOG performance status of 1 (meaning the patient was unable to do strenuous activities but were able to perform light housework and activities while sitting; 46% and 49%) compared with patients in the younger than 65 (31% and 31%) and 65 years and older but younger than 75 (46% and 39%) groups. Moreover, more patients in the younger than 65 group had de novo disease (the first occurrence of cancer in the body; 43% and 43%) compared with those 65 years and older but younger than 75 (38% and 37%) and 75 years and older groups (38% and 36%).

Across each treatment arm and patient age group, anywhere from 73% to 90% of patients received any subsequent therapy. Endocrine therapy alone was the most common subsequent treatment for patients in the Kisqali arm across all age groups. The most common first subsequent therapy in the placebo arm was any chemotherapy in all age groups except the 65 years and older but younger than 75 group, in which the most frequent subsequent therapy was endocrine therapy alone.

The incidence of any side effects and side effects of special interest were comparable across all patient subgroups and were typically manageable with standard dose modifications. Common side effects of special interest and of any severity included neutropenia (lower than normal number of neutrophils, a type of white blood cell) in 63% to 79% of patients who received Kisqali and 4% to 8% of those who received placebo.

In the Kisqali and placebo arms, respectively, the highest treatment discontinuation following side effect rates were observed in the 75 years and older group (41% versus 8%). Treatment discontinuation in the experimental arm was generally the result of liver enzyme level increases. The rate of patients who discontinued treatment in the Kisqali arm due to side effects without prior dose reduction was 34% in the younger than 65 years group, 41% in the 65 and older but younger than 75 group, and 50% in the 75 and older group.

The experimental regimen yielded a time to definitive deterioration benefit across all age groups with respect to pain score and fatigue score. Time to definitive deterioration was comparable between treatment arms in the 75 years and older group with respect to global health status and physical functioning; a more notable benefit in these outcomes with the Kisqali combination occurred in the other age groups.

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