News & Perspective

FDA expands the approval of ribociclib through new pilot programs

8 months ago, OP Editor

Ribociclib was initially approved by the US Food and Drug Administration (FDA) and European Commission in 2017 for use in combination with an aromatase inhibitor (AI) to treat postmenopausal women who are eligible.1,2 Based on phase III MONALEESA-7 trial results, ribociclib has now been granted approval by the FDA for use in combination with an AI as first-line therapy for treating HR+/HER2- advanced or metastatic breast cancer in pre/perimenopausal women.1 Additionally, ribociclib in combination with fulvestrant has also been approved by the FDA for treating postmenopausal women with HR+/HER2- advanced or metastatic breast cancer as both initial or second-line therapy based on phase III MONALEESA-3 trial findings.1,3

The MONALEESA (Mammary ONcology Assessment of LEE011 [ribociclib] Efficacy and SAfety) program is the largest industry sponsored phase III global clinical program investigating the efficacy and safety of ribociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, in HR+/HER2- advanced breast cancer, with more than 2,000 patients enrolled in the current trials.2,4

MONALEESA-7, a randomized, double-blind, placebo-controlled trial enrolled pre/perimenopausal women aged between 25 and 58 years with HR+/HER2- advanced or metastatic breast cancer who had not received any prior endocrine treatment for their advanced disease.3 Patients were randomized to receive either ribociclib in combination with tamoxifen or a nonsteroidal AI plus goserelin (ribociclib arm), or endocrine treatment alone plus goserelin (placebo arm).5

Results from the pre-specified nonsteroidal AI-only subgroup consisting of 495 participants showed the median progression-free survival (PFS) of 27.5 months for patients on the ribociclib arm compared with 13.8 months for those on the placebo arm (HR=0.569; 95% CI: 0.436-0.743).2 In contrast, the benefit of adding ribociclib to tamoxifen was found to be lower – only 11.1-month delay in disease progression or death compared to tamoxifen alone.3 The most frequently reported adverse event (AE) for both the arms was neutropenia.6

In MONALEESA-3 trial, 726 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who had received no or a maximum of one prior endocrine therapy for their advanced disease were enrolled. The participants were randomized 2:1 to receive either ribociclib and fulvestrant (ribociclib arm) or fulvestrant only (placebo arm).4 Median PFS was significantly improved with the addition of ribociclib to fulvestrant, whereby the median PFS for ribociclib arm was 20.5 months compared with 12.8 months for the placebo arm (HR=0.593; 95% CI: 0.480-0.732; p<0.001).4 The most frequently reported all-grade AEs for both the arms included neutropenia, nausea, and fatigue.4

With the new approvals, ribociclib is now the only CDK4/6 inhibitor indicated for use in combination with an AI as first-line therapy for women with HR+/HER2- advanced or metastatic breast cancer regardless of their menopausal status, or with fulvestrant as both initial or second-line therapy for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer.2,7

“Premenopausal women diagnosed with advanced breast cancer often face unique social challenges and a poorer prognosis. For the first time in nearly 20 years, we have results from a dedicated clinical trial among these women”, Jennifer Merschdorf, CEO of the Young Survival Coalition said. “With this approval, some younger women now have a new therapy indicated specifically for them that may help extend their lives without progression of disease”.3

Moreover, this is the first approval that the FDA has granted as a part of two new pilot programs, Real-Time Oncology Review and Assessment Aid, whereby it took less than a month for granting the approval after the submission of application.5 These novel pilot programs comprehensively aim to make the development and review of cancer drugs more efficient, while ameliorating FDA’s rigorous standard for evaluating efficacy and safety.5 “Based on phase III trial results that consistently showed clinical benefit, physicians should be encouraged to re-evaluate treatment for advanced breast cancer in the first-line setting”, said Dr. Dennis J. Salmon, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center, US.2



  1. FDA approves first cancer drug through new oncology review pilot that enables greater development efficiency. FDA News Release. 2018 (Accessed August 14, 2018, at
  2. Novartis Kisqali now first and only CDK4/6 inhibitor indicated in US as first-line therapy specifically for premenopausal women; and as initial therapy with fulvestrant in postmenopausal women. Global Novartis News Archive. 2018 (Accessed August 14, 2018, at
  3. Two New Indications of Kisqali Approved in US for Advanced Breast Cancers. BREAST CANCER NEWS. 2018 (Accessed August 14, 2018, at
  4. Slamon DJ, Neven P, Chia S, et al. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465-2472.
  5. Ribociclib Granted Expanded FDA Approval in Breast Cancer. Targeted Oncology. 2018 (Accessed August 14, 2018, at
  6. MONALEESA-7 Data Shows Ribociclib Active in Premenopausal Breast Cancer Subgroups. Targeted Oncology. 2018 (Accessed August 14, 2018, at
  7. Novartis MONALEESA-7 trial of Kisqali in advanced/metastatic breast cancer meets primary endpoint. PHARMABIZ. 2017 (Accessed August 14, 2018, at


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