FDA Grants Approval to Co-Packaging of Ribociclib With Letrozole for Metastatic Breast Cancer


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Florida Cancer Specialists

The FDA has given its approval to co-packaging of the oral medications ribociclib (Kisqali) and letrozole (Femara) for the treatment of postmenopausal women with HR-positive, HER2-negative advanced breast cancer.

The FDA has granted its approval to co-packaging of the oral medications ribociclib (Kisqali) and letrozole (Femara) for the treatment of postmenopausal women with HR-positive, HER2-negative advanced breast cancer.

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 1-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).

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

At a median follow-up of 15.3 months, the ribociclib group&rsquo;s median progression-free survival (PFS) had yet to be reached, whereas the placebo group had an estimated median PFS of 14.7 months. Blinded PFS assessment by an independent review committee resulted in a hazard ratio of 0.59 in favor of the ribociclib arm (P= .002).

After an additional 11 months of follow-up, a subsequent analysis showed that the median PFS was 25.3 months with the ribociclib combination versus 16 months with letrozole alone. Overall survival data are still not mature.

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 &ge;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 & Research Institute, 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.


  1. Hortobagyi GN, Stemmer SM, Burris HA, et al. First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA1.
  2. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer [published online October 8, 2016].N Engl J Med. doi:10.1056/NEJMoa1609709.
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