Adding the CDK4/6 inhibitor ribociclib to letrozole improved progression-free survival in postmenopausal women with hormone receptor-positive advanced breast cancer, researchers reported at the ESMO 2016 Congress in Copenhagen.
One of the highlights at this year’s ESMO Congress was the presentation of data from the Monaleesa-2 trial: this is the first-line treatment of advanced, HP-positive, HER2-negative breast cancer in which patients received the selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6) ribociclib in combination with letrozole as first-line therapy. The randomized, placebo-controlled, double-blind, multicenter study compared efficacy and safety of this combination with aromatase inhibitor monotherapy.
Many cancers with overexpression of CDK.
Ribociclib is administered orally. By specifically blocking CDK4/6, the compound inhibits phosphorylation of the retinoblastoma protein, a tumor suppressor protein whose function is impaired in many tumor types. Thus, the CDK-mediated transition from G1 to S phase of cell division is prevented. The cell cycle is interrupted, DNA synthesis is suppressed and tumor growth is inhibited. Overexpression of CDK is observed in many cancers, leading to dysregulation in the cell cycle.
Therapy options significantly expanded
The first interim analysis of data from the Monaleesa-2 trial showed a 44% improvement in the primary objective of progression-free survival compared to the placebo arm (HR: 0.556, p=0.00000329). Median progression-free survival was 14.7 months in the placebo arm but was not achieved in the ribociclib arm at data cutoff. Patients with measurable disease showed significantly higher objective response rates to ribociclib plus letrozole (53% vs. 37%, p=0.00028) and improved clinical benefit rates (80% vs. 72%, p=0.02) compared to letrozole alone.
In addition to the excellent oncological response, the data also confirm good tolerability. CDK4/6 inhibitors significantly expand the spectrum of therapeutic options in metastatic breast cancer.
Source: ESMO 2016 Congress, October 7-11, 2016, Copenhagen.
InFo ONCOLOGY & HEMATOLOGY 2016; 4(7-8): 3.
