FDA Approves Co-Packaging of Ribociclib With Letrozole to Treat MBC

FDA Approves Co-Packaging of Ribociclib With Letrozole to Treat MBC

The FDA has approved co-packaging of the oral medications ribociclib (Kisqali) and letrozole (Femara) that are used to treat HR-positive, HER2-negative advanced breast cancer in postmenopausal women.

With the new Kisqali® Femara® Co-Pack, patients can obtain a full 28-day cycle of the 2 medicines in 1 package with 1 prescription and 1 copay, and the cost will be the same as that for Kisqali alone, according to Novartis, which manufactures both medications.

“Providing physicians a convenient one-package prescribing option for their patients underscores our commitment to deliver innovative treatment solutions to the metastatic breast cancer community,” said Bill Hinshaw, executive vice president and US head of Novartis Oncology, in a statement announcing the approval.

The company noted that ribociclib, which helps to slow cancer progression by inhibiting the cyclin-dependent kinase 4 and 6 (CDK 4/6) proteins, can continue to be prescribed separately along with another aromatase inhibitor (AI).

The CDK 4/6 inhibitor ribociclib was approved by the FDA March 13 for use in combination with an AI for this population of women, based on findings for the phase III MONALEESA-2 trial. In that study, the combination reduced the risk of progression or death by 44% compared with letrozole alone in the first-line setting for HR+/HER2- advanced breast cancer (HR, 0.556; 95% CI, 0.43-0.72; P <.0001).

Additionally, 53% of patients with measurable disease who received the ribociclib-letrozole combination experienced a reduction in tumor burden of at least 30%.

“This is a significant result for women with this serious form of breast cancer," according to MONALEESA-2 principal investigator Gabriel N. Hortobagyi, MD, professor of medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center.

In the trial, ribociclib did add to treatment-associated toxicity, as 59.3% of patients who received the CDK 4/6 inhibitor developed grade 3/4 neutropenia, as compared with 0.9% of patients who received placebo. Grade 3/4 leukopenia occurred in 21% of the ribociclib arm and 0.6% of the placebo group. Hematologic adverse events were uncomplicated and resolved without incident in most cases.

The most common nonhematologic adverse events (all grades) were nausea (51.5% with ribociclib vs 28.5% with placebo), infections (50.3% vs 42.4%), fatigue (36.5% vs 30.0%), and diarrhea (35% vs 22.1%). The events were grade 1/2 severity in most cases.

MONALEESA-2 represents a paradigm shift for the management of HR+/HER2- advanced breast cancer, because at some point, all breast cancers will become resistant to endocrine therapy alone.

The CDK 4/6 inhibitor also proved effective in a subgroup of patients in this trial of women aged ≥65 years. The novel regimen was well tolerated among a MONALEESA-2 elderly subgroup, with a safety profile similar to that of the overall study population. Despite a higher rate of patients with an ECOG performance status of 1, the elderly population also had dose interruption and reduction rates consistent with the overall trial results, reported Lowell L. Hart, MD, of Florida Cancer Specialists, at the 2017 Miami Breast Cancer Conference.

The new co-pack is available in 3 ribociclib dosages (600 mg, 400 mg, or 200 mg), and each co-pack will also contain letrozole at the 2.5 mg dose. Novartis announced that the co-pack will be available domestically later this month at both specialty and retail pharmacies, and does not change the indication for either medicine.