By Peggy Peck, Editor-in-Chief, BreakingMED

CHICAGO — Adding the CDK4/6 inhibitor ribociclib to endocrine therapy significantly extended overall survival in younger women with advanced HR+/HER- breast cancer “with a 29% lower risk of death (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test),” investigators with the MONALEESA-7 trial reported here.

Sara Hurvitz, MD, of the UCLA Janssen Comprehensive Cancer Center, noted that this is the first study to focus exclusively on premenopausal women — a significant distinction, since breast cancer is a leading cause of cancer mortality in women younger than 45.

“This is the first study to demonstrate improved survival for a targeted therapy,” Hurvitz said at an American Society of Clinical Oncology press conference.

Among the findings:

  • “The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5-76.0) in the ribociclib group and 46.0% (95% CI, 32.0-58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54-0.95; P = 0.00973 by log-rank test).
  • The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the over-all intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50-0.98).
  • The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group).
  • The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55-0.87).”

MONALEESA-7, which compared ribociclib to first-line endocrine therapy, is the latest in the MONALEESA series that included the pivotal trials that paved the way for FDA approval of ribociclib for treatment of metastatic breast cancer in pre-, peri-, and postmenopausal women. Hurvitz noted that the MONALEESA findings on progression-free survival — which also favored ribociclib— were published last year in Lancet Oncology.

In addition to its presentation here as a featured late-breaking clinical trial, the MONALEESA 7 overall survival findings will be published online in The New England Journal of Medicine.

ASCO breast cancer spokesperson Harold J. Burstein, MD, PhD of the Dana-Farber Cancer Institute in Boston, told BreakingMED that the survival benefit seen in MONALEESA-7 is likely to extend to all currently approved CDK4/6 inhibitors, palbociclib (Ibrance), abemaciclib (Verzenio), and ribociclib (Kisqali), all three of which are “well-known in the U.S. oncology community.” Moreover, the drugs have the advantage of “being oral and therefore portable, so they are an appealing option.” But he added that overall survival benefit may prove to be a game-changer outside the U.S., where CDK4/6 inhibitors are not so widely used: “this could tip the scale worldwide.”

That said, the findings from MONALEESA-7 do contrast with overall survival seen in PALOMA 3, which found that palbociclib did not extend survival beyond what was seen in a placebo. MONALEESA-7 lead investigator, Dapu Tripathy, MD, professor and chair of Breast Medical Oncology, University of Texas MD Anderson Cancer Center in Houston, told BreakingMED that there were a number of key differences that make a cross trial comparison problematic. “PALOMA-3 trial included premenopausal and post-menopausal patients who were more heavily pre-treated, whereas all patients in the MONALEESA-7 trial were premenopausal or perimenopausal and were receiving initial endocrine therapy.”

It is also possible, he added, that all “CDK inhibitors are really not alike…ribociclib may have a different level of selectivity for other cyclin-dependent kinase complexes than the other CDK4/6 inhibitors, and it has been hypothesized that such differences could potentially be clinically relevant.”

Thus, although Burstein suggested that the survival benefit demonstrated by ribociclib is evidence of a class effect, neither Hurvitz nor Tripathy were ready to draw the same conclusion. Hurvitz pointed out that “only ribociclib now has evidence of an overall survival benefit … the others have not demonstrated the benefit in clinical trials.” And, Tripathy added that the MONALEESA-7 results may make clinicians — and patients — opt for ribociclib as a preferred choice among CDK4/6 inhibitors.

However, he cautioned that MONALEESA-7 is just one trial, “so if you ask me ‘can this change guidelines,’ I will say no. We need more trials to do that … this is certainly something to consider and discuss as we make treatment decisions, but it’s too early to consider a guideline change.”

MONALEESA-7 enrolled 672 patients all of whom received endocrine therapy (goserelin plus either an aromatase inhibitor or tamoxifen) plus ribociclib 600 mg/day (3-weeks on, 1 week off) or matched placebo.

The overall survival benefit emerged from a prespecified interim analysis of overall survival that was triggered when the mortality threshold of 192 deaths was reached — 83 deaths among the 335 patients treated with ribociclib and 109 in the 337-patient placebo arm.



The MONALEESA 7 study was funded by Novartis.

Hurvitz disclosed travel, accommodations, expenses from Novartis, Lilly, OBI Pharma, Research Funding (Institutional) from Genentech/Roche, Novartis, GlaxoSmithKline, Boehringer Ingelheim, Sanofi, Pfizer, Amgen, OBI Pharma, Puma Biotechnology, Dignitana, Bayer, Biomarin, Lilly, Merrimack, Medivation, Cascadian Therapeutics, Seattle Genetics, Daiichi Sankyo, Macrogenics, and Ambryx.

Burstein had no disclosures.

Tripathy reported grants and personal fees from Novartis, during the conduct of the study; personal fees from Polyphor, personal fees from Genomic Health, personal fees from Sellas Life Sciences, personal fees from Pfizer, outside the submitted work.



Hurvitz SS, et al “Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: Overall survival (OS) results” ASCO 2019; Abstract LBA1008.

Im SA, et al “Overall survival with ribociclib plus endocrine therapy in breast cancer” N Engl J Med 2019; Published online June 4 DOI: 10.1056/NEJMoa1903765.


Peggy Peck, Editor-in-Chief at BreakingMED, a service of @Point of Care, LLC, which provides daily medical news reports curated to serve the unique needs of busy physicians and other healthcare professionals.