Pierfranco Conte, MD
The FDA recently approved ribociclib (Kisqali) for use in combination with an aromatase inhibitor as initial therapy for treatment of postmenopausal women with HR+/HER2-negative advanced or metastatic breast cancer.
Ribociclib, an inhibitor of CDK4/6, was approved based on data from the phase III MONALEESA-2 trial, which was ended early following the first preplanned interim analysis. In this analysis, the combination of ribociclib and the aromatase inhibitor letrozole met the trial’s primary endpoint by demonstrating statistically significant improvement in progression-free survival (PFS) compared to letrozole alone.
The randomized, double-blind MONALEESA-2 study showed a 44% improvement in PFS with the ribociclib combination (HR, 0.556; P
<.0001). Median PFS was not reached in the ribociclib arm (95% CI, 19.3 months - not reached) at data cut-off compared to 14.7 months (95% CI, 13.0-16.5) in the letrozole/placebo arm.
According to data reported at the 15th St Gallen Breast Cancer Conference, the response to ribociclib was unaffected by either prior endocrine treatment or prior chemotherapy.
“It was unclear whether endocrine therapy, a standard adjuvant therapy for HR-positive, HER2-negative breast cancer may alter disease biology or response to subsequent therapy. Here we report on patients who received neoadjuvant endocrine therapy or chemotherapy prior to entering the MONALEESA-2 phase III study of first-line ribociclib,” said, Pierfranco Conte, MD, University of Padova and Instituto Oncologico Veneto, in Padova, Italy.
“It is estimated that approximately 30% of patients presenting with nonmetastatic breast cancer at the initial diagnosis will eventually relapse following standard treatments and require subsequent treatment,” he noted.
MONALEESA-2 randomized 668 postmenopausal treatment-naïve women with HR+, HER2-negative advanced breast cancer to ribociclib at 600 mg/day, 3 weeks on/1 week off plus letrozole at 2.5 mg/day, continuous, or the same dose of continuous letrozole plus placebo.
Of the overall population in the MONALEESA-2 trial, 146 (43.7%) patients in the ribociclib plus letrozole and 145 (43.4%) patients in the letrozole/placebo arm had received prior chemotherapy and 175 (52.4%) versus 171 (51.2%) patients in the respective treatment arms had received prior endocrine therapy; 123 (36.8%) versus 120 (35.9%) patients in the respective arms had received both chemotherapy and endocrine therapy.
Conte and colleagues conducted this preplanned subgroup analysis, which demonstrated that risk reduction in patients receiving prior chemotherapy was consistent with the entire population (HR, 0.548; 95% CI, 0.384-0.780), as was the risk reduction in patients receiving prior endocrine therapy (HR, 0.538; 95% CI, 0.384-0.754).
Similar results were observed in patients receiving no prior chemotherapy with ribociclib/letrozole versus placebo/letrozole (HR, 0.548; 95% CI, 0.373-0.806) or endocrine therapy, (HR, 0.570; 95% CI, 0.380-0.854).
In the cohort of patients having prior chemotherapy or endocrine therapy, ribociclib/letrozole increased PFS versus letrozole/placebo; median PFS was 19.3 months with ribociclib/letrozole compared to 13 months with letrozole/placebo in each prior treatment subgroup. Previously untreated patients showed a median PFS of not reached with ribociclib/letrozole versus 19.3 months with placebo/letrozole in both subgroups.
In the ribociclib/letrozole treatment arm, patients with either prior chemotherapy or endocrine therapy showed a best overall response of 38% compared to 43% in patients receiving no prior treatment.
“Safety data were consistent across subgroups and the full population,” Conte remarked. Neutropenia occurred in 59% of patients in the ribociclib arm compared to 1% of the placebo arm, leukopenia occurred in 21% versus 1%, lymphopenia in 7% versus 1%, and patients in the respective treatment arms and patients in the ribociclib arm had a higher incidence of elevated alanine aminotransferase and elevated aspartate aminotransferase.
“The safety profile was also similar to the overall population among patients receiving ribociclib plus letrozole who had undergone prior chemotherapy or endocrine therapy,” said Conte.<<<
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