The Best Results Achieved So Far in the Treatment of Stage 4 Breast Cancer

ESMO (European Society for Medical Oncology) Congress 2021: according to the results of a comprehensive clinical trial presented there, for postmenopausal hormone receptor (HR)-positive / human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, when the aromatase inhibitor letrozole was given with the CDK 4/6 inhibitor ribosiklib (Valamor), median overall survival improved by 12 months.

The First Study to Show Survival Exceeding 5 Years in Metastatic Breast Cancer

MONALEESA-2 was a clinical trial in which hormone suppression therapy with letrozol was being received by 668 patients, who were randomly assigned 1:1 to two groups; the experimental group received ribosiklib and the control group received placebo.

At the ESMO 2021 Congress, in the context of first-line treatment of metastatic breast cancer, FDA approval of ribosiklib in 2017 was based on the MONALEESA-2 study, whose final overall survival results were presented.

Notable Results

• At a median follow-up of 6.6 years, median overall survival was 63.9 months with ribosiklib versus 51.4 months in the placebo arm.
• This improvement in survival corresponds to a 24% reduction in the relative risk of death ( P = .004).
• The estimated 6-year overall survival rate was 44.2% with ribosiklib and 32.0% with placebo.

This is the first evidence showing median overall survival exceeding 5 years in a phase 3 clinical trial for advanced breast cancer.

CDK 4/6 Inhibitors Have Changed the Approach to Breast Cancer Treatment

The concept of "treatment without chemotherapy" has become established in hormone-positive breast cancer.

The drugs we have discussed most over the past 5 years in the treatment of hormone-positive breast cancer are CDK 4/6 inhibitors. These drugs act as inhibitors of the mitosis (cell division) cycle, and there are 3 internationally approved drugs in this group with similar mechanisms of action: palbosiklib (Reampla), ribosiklib (Valamor) and abemasiklib (Yulareb). In this group, palbosiklib (US brand name Ibrance, Reampla in Turkey) was the first drug to receive approval in 2015 for patients with breast cancer from the US Food and Drug Administration (FDA). Later, abemasiklib (not yet reimbursed in Turkey) and ribosiklib (US brand name Kisqali, Valamor in Turkey) received FDA approvals in 2017. These drugs were approved and licensed in 2019 by Turkey's Ministry of Health for use in patients with breast cancer.

The combination of standard hormonal therapy for breast cancer with a CDK 4/6 inhibitor is currently considered the standard first-line breast cancer treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer; that is, concurrent administration of a CDK 4 / 6 inhibitor (e.g., palbociclib, ribociclib, abemaciclib) with an aromatase inhibitor or fulvestrant .

The truly impressive results of the MONALEESA-2 study support the frontline use of CDK 4/6 inhibitors such as ribosiklib.

Ribosiklib and other CDK 4/6 inhibitors have shown consistent progression-free survival benefit in metastatic disease, but ribosiklib is the first of the major phase 3 trials with definitive overall survival results. These results had been awaited for a long time.

The overall survival benefit in MONALESSA-2 began to emerge at around month 20 and continued to increase over time.

Among other benefits, median time to first chemotherapy was 50.6 months with ribosiklib versus 38.9 months with placebo; patients therefore "gained a year before starting chemotherapy.

No new side effects were observed for ribosiklib in the trial. The most common side effects were neutropenia and liver function abnormalities, but these were largely asymptomatic laboratory findings and were fully reversible. Most patients treated with ribosiklib had a twofold prolongation of the QT interval on ECG (heart tracing), but again no clinical consequences of this finding were identified. Interstitial lung disease developed in less than 1% of patients in the ribosiklib arm. Most of these side effects occurred in the first 12 months of treatment.