FDA Expands Ribociclib Indication in Hormone Receptor–Positive, HER2-Negative Advanced or Metastatic Breast Cancer

Today, the U.S. Food and Drug Administration (FDA) expanded the indication for ribociclib (Kisqali) in combination with an aromatase inhibitor for premenopausal or perimenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer as initial endocrine-based therapy. The FDA also approved ribociclib in combination with fulvestrant (Faslodex) for postmenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer as initial endocrine-based therapy or following disease progression on endocrine therapy.

Ribociclib was previously approved for postmenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine therapy. 

MONALEESA-7 and MONALEESA-3   

The efficacy of ribociclib in combination with an aromatase inhibitor for pre- or perimenopausal women was based on MONALEESA-7, a randomized, double-blind, placebo-controlled trial. Pre- or perimenopausal women were randomized to ribociclib plus either a nonsteroidal aromatase inhibitor or tamoxifen and goserelin (Zoladex) vs placebo plus either a nonsteroidal aromatase inhibitor or tamoxifen and goserelin.

Results from the prespecified nonsteroidal aromatase inhibitor–only subgroup of 495 pre- or perimenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer who received no prior endocrine therapy for advanced disease showed an estimated median progression-free survival (Response Evaluation Criteria in Solid Tumors, version 1.1) of 27.5 months for patients on the ribociclib arm compared with 13.8 months for those on the placebo arm (hazard ratio [HR] = 0.569, 95% confidence interval [CI] = 0.436–0.743). Ribociclib is not indicated for concomitant use with tamoxifen.

The efficacy of ribociclib in combination with fulvestrant was demonstrated in MONALEESA-3, a randomized double-blind, placebo-controlled trial of ribociclib in combination with fulvestrant in 726 postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer who received no or only one line of prior endocrine treatment. The estimated median progression-free survival was 20.5 months for patients taking ribociclib compared with 12.8 months for those who received placebo (HR = 0.593, 95% CI = 0.480–0.732; P < .0001).

The most common adverse reactions in at least 20% of patients were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash, and cough.

The recommended starting ribociclib dose is 600 mg orally (three 200-mg tablets) once daily with or without food for 21 consecutive days followed by 7 days off treatment.

First Approval Under Pilot Programs

This is the first FDA approval using the Real Time Oncology Review and the Assessment Aid, pilot programs that enabled the FDA review team to begin analyzing data before the application submission. With this real-time review, the FDA was able to start evaluating the clinical data as soon as the trial results became available, enabling the agency to be ready to approve the new indication upon filing of a formal application. The FDA was able to approve the application less than 1 month after it was submitted.

The Real Time Oncology Review program focuses on early submission of data that are the most relevant to assessing safety and effectiveness of the product. Then, when the sponsor submits the application with the FDA, the review team will already be familiar with the data and in a better position to conduct a more efficient, timely, and thorough review.

The second program is a new templated Assessment Aid that the applicant uses to organize its submission into a structured format to facilitate the FDA’s review of the application. By using a structured template, the FDA is able to layer its assessment into the same file submitted by the sponsor, allowing this annotated application to serve as the document that contains the FDA review. This voluntary submission form provides for a more streamlined approach to reviewing data and illustrating FDA’s analysis. It allows for drug reviewers to focus on the key benefit-risk and labeling issues, rather than administrative issues.

Currently, the two pilot programs are being used for supplemental applications for already-approved cancer drugs but could later be expanded to original drugs and biologics.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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