Meeting NewsPerspective

Ribociclib plus endocrine therapy improves survival in advanced breast cancer subtype

Sara Hurvitz
Sara A. Hurvitz

CHICAGO — Premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer derived a significant survival benefit from the addition of ribociclib to endocrine therapy, according to the most recent OS results from the randomized phase 3 MONALEESA-7 study presented at ASCO Annual Meeting.

“This study is unique because it’s the only trial that exclusively enrolled young women — pre- or perimenopausal women younger than 59 [years],” lead author Sara A. Hurvitz, MD, director of the breast cancer clinical research program at UCLA Jonsson Comprehensive Cancer Center, said in an interview with HemOnc Today. “We wanted to do this study because young women represent about 20% of all breast cancers in women younger than 50 [years]. They have worse survival and more aggressive disease biology compared with older women.”

Ribociclib (Kisqali, Novartis), a CDK4/6 inhibitor, received FDA approval in July 2018 for use with an aromatase inhibitor by pre- or perimenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. This approval was based on earlier results from the randomized, double-blind MONALEESA-7 trial, which enrolled 672 premenopausal women with this form of advanced breast cancer who received goserelin (Zoladex; TerSera AstraZeneca) with ribociclib (n = 335) or placebo (n = 337). All women also received a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen.

The analysis is the second of three protocol-specific analyses of OS scheduled to occur after approximately 189 deaths (75% of planned total events). The prespecified interim analysis had a data cutoff of Nov. 30, 2018, with a median follow-up of 34.6 months (minimum, 28 months).

At data cutoff, 173 patients remained on treatment (ribociclib, n = 116 [35%]; placebo, n = 57 [17%]). Researchers assessed OS after 192 deaths (ribociclib, n = 83; placebo, n = 109).

Results showed significantly longer median OS with ribociclib and endocrine therapy vs. placebo and endocrine therapy (not reached vs. 40.9 months, HR = 0.71; 95% CI, 0.53-0.94), representing a 29% relative reduction in risk for death. This crossed the prespecified stopping boundary for superior efficacy
OS rate with ribociclib and endocrine therapy was 70.2% vs. 46% with placebo and endocrine therapy.

Among women treated with a nonsteroidal aromatase inhibitor, researchers observed sustained OS improvement in the ribociclib vs. placebo group (not reached vs. 40.7 months; HR = 0.69; 95% CI, 0.5-0.98). The two groups demonstrated similar rates of post-treatment therapy use (68.9% vs. 73.2%).

Among women treated with tamoxifen, median OS was not reached for those who also received ribociclib or placebo (HR = 0.79; 95% CI, 0.45-1.37).

Researchers are analyzing patient-reported outcomes as well as biomarkers and circulating tumor DNA to identify which women could benefit most from ribociclib.

“The impact of these findings will likely be large, because hormone receptor breast cancer comprises two-thirds of all breast cancers diagnosed,” Hurwitz told HemOnc Today. “This is not a small subset of patients. We do have three drugs approved in this indication, and the MONALEESA-7 study is the first study to show a significant improvement in OS.” – by Jennifer Byrne

Reference:

Hurvitz S, et al. Abstract LBA1008. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: The study received funding from Novartis. Hurvitz reports travel accommodations and expenses from Eli Lilly, Novartis and OBI Pharma; and research funding to her institution from Amgen, Ambryx, Bayer, Biomarin, Boehringer Ingelheim, Cascadian Therapeutics, Daiichi Sankyo, Dignitana Genentech/Roche, GlaxoSmithKline, Eli Lilly, Macrogenics, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology and Seattle Genetics. Please see the abstract for all other authors’ relevant financial disclosures.

Sara Hurvitz
Sara A. Hurvitz

CHICAGO — Premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer derived a significant survival benefit from the addition of ribociclib to endocrine therapy, according to the most recent OS results from the randomized phase 3 MONALEESA-7 study presented at ASCO Annual Meeting.

“This study is unique because it’s the only trial that exclusively enrolled young women — pre- or perimenopausal women younger than 59 [years],” lead author Sara A. Hurvitz, MD, director of the breast cancer clinical research program at UCLA Jonsson Comprehensive Cancer Center, said in an interview with HemOnc Today. “We wanted to do this study because young women represent about 20% of all breast cancers in women younger than 50 [years]. They have worse survival and more aggressive disease biology compared with older women.”

Ribociclib (Kisqali, Novartis), a CDK4/6 inhibitor, received FDA approval in July 2018 for use with an aromatase inhibitor by pre- or perimenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. This approval was based on earlier results from the randomized, double-blind MONALEESA-7 trial, which enrolled 672 premenopausal women with this form of advanced breast cancer who received goserelin (Zoladex; TerSera AstraZeneca) with ribociclib (n = 335) or placebo (n = 337). All women also received a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen.

The analysis is the second of three protocol-specific analyses of OS scheduled to occur after approximately 189 deaths (75% of planned total events). The prespecified interim analysis had a data cutoff of Nov. 30, 2018, with a median follow-up of 34.6 months (minimum, 28 months).

At data cutoff, 173 patients remained on treatment (ribociclib, n = 116 [35%]; placebo, n = 57 [17%]). Researchers assessed OS after 192 deaths (ribociclib, n = 83; placebo, n = 109).

Results showed significantly longer median OS with ribociclib and endocrine therapy vs. placebo and endocrine therapy (not reached vs. 40.9 months, HR = 0.71; 95% CI, 0.53-0.94), representing a 29% relative reduction in risk for death. This crossed the prespecified stopping boundary for superior efficacy
OS rate with ribociclib and endocrine therapy was 70.2% vs. 46% with placebo and endocrine therapy.

Among women treated with a nonsteroidal aromatase inhibitor, researchers observed sustained OS improvement in the ribociclib vs. placebo group (not reached vs. 40.7 months; HR = 0.69; 95% CI, 0.5-0.98). The two groups demonstrated similar rates of post-treatment therapy use (68.9% vs. 73.2%).

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Among women treated with tamoxifen, median OS was not reached for those who also received ribociclib or placebo (HR = 0.79; 95% CI, 0.45-1.37).

Researchers are analyzing patient-reported outcomes as well as biomarkers and circulating tumor DNA to identify which women could benefit most from ribociclib.

“The impact of these findings will likely be large, because hormone receptor breast cancer comprises two-thirds of all breast cancers diagnosed,” Hurwitz told HemOnc Today. “This is not a small subset of patients. We do have three drugs approved in this indication, and the MONALEESA-7 study is the first study to show a significant improvement in OS.” – by Jennifer Byrne

Reference:

Hurvitz S, et al. Abstract LBA1008. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: The study received funding from Novartis. Hurvitz reports travel accommodations and expenses from Eli Lilly, Novartis and OBI Pharma; and research funding to her institution from Amgen, Ambryx, Bayer, Biomarin, Boehringer Ingelheim, Cascadian Therapeutics, Daiichi Sankyo, Dignitana Genentech/Roche, GlaxoSmithKline, Eli Lilly, Macrogenics, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Puma Biotechnology and Seattle Genetics. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective
    Debra Patt

    Debra Patt

    Those of us who see and treat patients with breast cancer know the advent of CDK 4/6 inhibitors for the treatment of patients with ER-positive metastatic breast cancer has been remarkable. We have so many patients who take endocrine therapy and a CDK 4/6 inhibitor and — for many years — we have been able to talk about the benefit in PFS, which is nearly triple for patients who receive this unique therapy.

    In the MONALEESA-7 trial — in which researchers studied ribociclib in combination with endocrine therapy for patients with advanced breast cancer — we not only saw a PFS benefit, as expected, but also an OS benefit. This confirms what we have suspected for a long time.

    In the space of CDK 4/6 inhibition we have three drugs — palbociclib (Ibrance, Pfizer), ribociclib and abemaciclib (Verzenio, Eli Lilly). They are different medications with different costs, dosing schedules and toxicities. But, they continue to be clinically meaningful in making advanced breast cancer a chronic disease for many of our patients.

    • Debra Patt, MD, MPH, MBA
    • Texas Oncology US Oncology Network McKesson Specialty Health

    Disclosures: Patt reports no relevant financial disclosures.

    Perspective
    Harold J. Burstein

    Harold J. Burstein

    The theme we are seeing in this presentation is that, with mature and robust data, we are now achieving substantial improvements in survival with the innovative drugs that are coming to our market. This is an important study because it shows that this widely used class of drugs, CDK 4/6 inhibitors, will delay the time to the need for chemotherapy for advanced breast cancer, and will really double the effectiveness of endocrine therapy. This now also translates into a significant survival benefit for women who have ER-positive metastatic breast cancer.

    It’s also significant because, as Dr. Hurvitz mentioned, this study focuses on a group of young women. Many people think of young women as having different types of breast cancer, like triple-negative breast cancer or HER2-positive breast cancer. In fact, the most common form of breast cancer in young women is ER-positive breast cancer. This is the largest study in recent memory that is focused exclusively on premenopausal women, and shows that they, too, benefit from this class of drugs in a remarkable way.

    Finally, in an era when we are thinking about value in oncology care, the demonstration of a robust survival difference substantially adds to a value proposition for products like ribociclib. So hopefully, these data will enable access to this product to more women around the world, particularly in health care systems that assess value rigorously as part of their decisions for national access to drugs.

    Overall, these are important survival data in a group of patients historically understudied, showing a clear benefit and establishing value of this class of drugs in the management of the most common form of breast cancer.

    • Harold J. Burstein, MD, PhD, FASCO
    • Dana-Farber Cancer Institute
      Brigham & Women’s Hospital

    Disclosures: Burstein reports no relevant financial disclosures.

    Perspective
    Kevin Kalinsky

    Kevin Kalinsky

    These data are exciting because, when adding targeted therapy to endocrine therapy, we are observing a survival benefit. We had known that there was an improvement in PFS but now we see, in the frontline setting with the CDK 4/6 inhibitor, improvement in survival.

    This is the only premenopausal-only study. To have achieved an OS benefit is quite remarkable in these frontline patients.

    This study will certainly change the consideration of CDK 4/6 inhibitors in frontline patients with premenopausal disease. Because we’d seen an improvement in PFS, our practice pattern has been to give hormonal therapy with the CDK 4/6 inhibitor upfront. However, there are other clinicians who would perhaps argue that we should wait to see if a survival benefit will be achieved. These data could convince these providers who haven’t been using it as frontline treatment that there is a survival benefit. That could be further compelling evidence that they might have been waiting for.

    The other remarkable finding of this study is the response rate. This is further evidence of how CDK 4/6 inhibitors have been paradigm-shifting. We used to think that we needed to start with chemotherapy in these patients, but this study shows quite remarkable responses with the combination of hormonal therapy and CDK 4/6 inhibitors. The kind of responses we’ve seen in this study will hopefully further compel treating physicians to use this combination.

    • Kevin Kalinsky, MD
    • New York-Presbyterian and Columbia University Medical Center

    Disclosures: Kalinsky reports speakers bureau roles with AstraZeneca, Eisai, El Lilly, Genentech, Ipsen, and Odonate Therapeutics; institutional support from Acetylon, Amgen, Calithera Biosciences, CytomX Therapeutics, Eli Lilly, Genentech, Novartis, Seattle Genetics and Zeno Pharmaceuticals; and employment of his spouse by Array Biopharma.

    Perspective
    Kristen D. Whitaker

    Kristen D. Whitaker

    To see improved OS with the addition of a CDK 4/6 inhibitor to endocrine therapy, especially in premenopausal women who often have aggressive disease, is really exciting for our patients.

    Improving OS with cancer therapies is the ultimate goal, but often hard to achieve. It’s excellent that we now have a CDK 4/6 inhibitor in our arsenal that hits the improved OS mark. It also may be helpful in the selection of the best CDK 4/6 inhibitor for premenopausal women.

    • Kristen D. Whitaker, MD
    • Fox Chase Cancer Center

    Disclosures: Whitaker reports no relevant financial disclosures.

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