TrialWatch: Novartis’ Ribociclib Plus Endocrine Therapy May Help Advanced Breast Cancer

Novartis drug ribociclib (Kisqali) may help women with advanced breast cancer. By combining ribociclib with endocrine therapy it extended progression-free survival (PFS) in women with hormone receptor-positive (HR+)/HER2—advanced breast cancer compared to endocrine therapy alone. The study findings are a the result of a subgroup analyses of the Phase 3 MONALEESA trials (MONALEESA -2,-3 and -7). The results showed that the combination increased survival compared with endocrine therapy alone.

The study findings (abstract P6-18-07) are the result of subgroup analyses of the phase 3 MONALEESA trials (MONALEESA-2, -3 and -7). The results showed that the combination increased survival compared with endocrine therapy alone, “regardless of the presence of visceral metastases,” the investigators reported. In patients with visceral metastases, “increased PFS benefit was seen regardless of burden of disease [=< 3 or > 3 lesions],” they said.

Slowing Metastasis
Visceral breast cancer metastases, such as to the lungs or liver, are often associated with a poor prognosis (Cancer Manag Res 2015;7:37-46). Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that helps slow the progression of cancer by inhibiting two proteins: cyclin-dependent kinase 4 and 6 (CDK4/6). “These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably,” according to a press release from Novartis.

“Nearly 60 percent of patients enrolled in the MONALEESA clinical trials had visceral metastases, and all benefited from treatment with ribociclib in combination with endocrine therapy,” said Denise Yardley, MD, a senior investigator of the Breast Cancer Research Program at Sarah Cannon Research Institute, in Nashville, Tenn. “These results, coupled with the National Comprehensive Cancer Network and Advanced Breast Cancer 4 recommended treatment guidelines for HR+ advanced breast cancer patients with visceral metastases, support the use of ribociclib combination therapy as a standard of care in this patient population,” noted Dr. Yardley, who was the principal investigator of the trial.

In patients with visceral metastases, ribociclib plus endocrine therapy extended median PFS by 11.5 months in MONALEESA-2 (24.9 vs. 13.4 months) and 13.4 months in MONALEESA-7 (23.8 vs. 10.4 months) compared with endocrine therapy alone. “Median PFS for patients with visceral metastases in the MONALEESA-3 trial still has not been reached compared to 16.5 months median PFS in patients receiving endocrine therapy alone,” according to the Novartis press release.

Improved Overall Response Noted
Improvement in overall response rate (ORR) also was demonstrated in the trials. “Across the MONALEESA trials in patients with visceral metastases and measurable disease, the [ORR] in patients who received ribociclib plus endocrine therapy compared to endocrine therapy alone was 53 percent versus 40 percent [MONALEESA-2], 50 percent versus 38 percent [MONALEESA-7] and 48 percent versus 31 percent [MONALEESA-3],” the researchers reported. Patients without visceral disease showed an ORR of 59 percent versus 35 percent, 52 percent versus 32 percent, and 49 percent versus 39 percent in MONALEESA-2, -7 and -3, respectively.