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Ribociclib Recommended for EU Approval in Frontline HR+/HER2- Breast Cancer

Jason Harris
Published: Friday, Jun 23, 2017

Bruno Strigini, CEO

Bruno Strigini

The Committee for Medicinal Products for Human Use (CHMP), a part of the European Medicines Agency (EMA), recommended approval of ribociclib (Kisqali) for use in combination with an aromatase inhibitor as a first-line treatment for postmenopausal women with hormone receptor (HR)-positive /HER2-negative locally advanced or metastatic breast cancer.

Ribociclib, in combination with an aromatase inhibitor, was shown to reduce the risk for disease progression or death by 44% compared with letrozole monotherapy.

The recommendation now goes to the European Commission, which is expected to make a final decision on full approval within 2 months. Approval would make the CDK 4/6 inhibitor available in all 28 European Union member states plus Iceland, Norway, and Liechtenstein.

“There is currently no cure for advanced breast cancer, and approximately 30% of those affected by early-stage breast cancer will go on to develop advanced disease,” Novartis Oncology CEO Bruno Strigini said in a press release. “This positive CHMP opinion brings us 1 step closer to improving the lives of women diagnosed with advanced or metastatic breast cancer throughout Europe.”

Worldwide, an estimated 250,000 women will be diagnosed with advanced breast cancer each year. Up to one-third of patients with early-stage breast cancer will progress to metastatic disease, which is currently incurable.

CHMP based its positive opinion on results from the global phase III MONALEESA-2 trial of 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy.1,2 The trial ended prematurely after an initial interim data analysis, performed after 243 qualifying events including progression or death, demonstrated a significant benefit in favor of the ribociclib arm.

The FDA approved ribociclib for use in the patient population based on the same results in March.

Ninety-three (27.8% of randomized patients) events occurred in the ribociclib arm compared with 150 (44.7%) in the placebo arm.

Patients were assigned to 2.5 mg daily of letrozole plus placebo or 600 mg daily of ribociclib for 3 weeks followed by 1 week off. The primary endpoint of the study was progression-free survival (PFS).

At a median follow-up of 15.3 months, median PFS in the ribociclib group had yet to be reached. Median PFS in the placebo group was an estimated 14.7 months. Blinded PFS assessment by an independent review committee resulted in a hazard ratio (HR) 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 (HR, 0.568; 95% CI, 0.457-0.704; P <.0001). Overall survival data are still not mature.

The 18-month PFS was 63% with ribociclib versus 42.2% for the placebo group. More than half of women with measurable disease taking ribociclib plus letrozole saw their tumor size shrink by at least 30%. The overall response rate (ORR) for these patients was 55% compared with 39% for letrozole alone (P = .00025).

Ribociclib was associated with substantially increased treatment-related adverse events (AEs). Almost 60% of patients in the experimental arm developed grade 3/4 neutropenia compared with 0.9% of patients assigned to placebo. Patients assigned to ribociclib were significantly more likely to experience grade 3/4 leukopenia, 21% versus 0.6%. Hematologic AEs were uncomplicated and resolved without incident in most cases.

The most common nonhematologic AEs (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. Rates of discontinuation were 7.5% with ribociclib and 2.1% with placebo.


  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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