SAN ANTONIO — The CDK4/6 inhibitor ribociclib (Kisqali, Novartis) dramatically improves progression-free survival (PFS) when added to endocrine therapy in ovarian-suppressed younger patients with hormone receptor-positive (HR+), human epidermal receptor 2-negative (HER2-) advanced breast cancer, according to first-of-its-kind data.
In short, it's beneficial to add the drug to what is an established first-line treatment for pre- and perimenopausal women with this type of breast cancer.
"MONALEESA-7 is the first clinical trial to have the statistical power to show that ribociclib has clinical benefit specifically for pre- and perimenopausal women," Debu Tripathy, MD, professor of medicine and chair of the department of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, said in a statement.
Ribociclib is "an important potential new treatment option for premenopausal patients with this type of advanced breast cancer," he added in a press briefing.
The study was reported here at the San Antonio Breast Cancer Symposium (SABCS) 2017.
In the MONALEESA-2 trial investigators showed that the addition of ribociclib to first-line endocrine prolonged PFS in postmenopausal women with HR+, HER2- advanced disease.
In the new phase 3 trial, Dr Tripathy and coinvestigators randomized 335 women to ribociclib plus endocrine therapy and 337 women to placebo plus endocrine therapy. Approximately one-quarter of the cohort received tamoxifen and the rest received an aromatase inhibitor. All patients were ovarian suppressed with the luteinizing hormone-releasing hormone, goserelin (Zoladex, AstraZeneca).
"Patient demographics were well balanced and the expected median age was low at 43 for the additional ribociclib group and 45 for the placebo group," Dr Tripathy noted.
The median follow-up at the cut-off point of the trial was 19.2 months.
At follow-up, median PFS in the ribociclib plus endocrine therapy group was 23.8 months compared with 13.0 months for the control group, suggesting that treatment with the additional CDK4/6 inhibitor effectively halved the risk for progression (hazard ratio, 0.55; P < .001).
The type of endocrine therapy patients received did not appear to have any effect on the superior PFS rate in the ribociclib arm either.
PFS Rates by Endocrine Therapy Partner
|Tamoxifen Plus Ribociclib||Tamoxifen Plus Placebo||Aromatase Inhibitor Plus Ribociclib||Aromatase Inhibitor Plus Placebo|
|Median PFS||22.1 months||11 months||27.5 months||13.8|
|PFS = progression-free survival; HR = hazard ratio|
In a separate analysis made by a blinded independent review committee, median PFS had not been reached at study cut-off in patients who received ribociclib compared with a median PFS of 11.1 months for the placebo arm.
"Benefits were also similar among key subgroups including age, race, estrogen-receptor status, liver or lung involvement, disease-free interval or prior chemotherapy for advanced disease," Dr Tripathy observed.
There were also significant differences in the secondary endpoint of overall response rate (40.9% in the ribociclib arm vs 29.7% in the placebo arm).
Far more interruptions in dose occurred in the CDK4/6 inhibitor arm, mostly due to adverse events (AEs). Approximately one-third of patients in the ribociclib arm also required a reduction in the dose.
Grade 3 and 4 neutropenia was the most common hematologic AE seen in association with the CDK4/6 inhibitor, occurring in approximately 60% of patients in the ribociclib arm. Febrile neutropenia was rare and occurred in only about 2% of patients.
Rates of nonhematologic toxicities were similar in both treatment groups; the most common were hot flushes and arthralgia, likely related to the use of tamoxifen or an aromatase inhibitor.
Discontinuation rates due to AEs were similar in both groups, at approximately 3%.
Importantly, patient-reported quality-of-life outcomes reflecting global health status showed that there was a sustained improvement in time to definitive deterioration in the ribociclib arm compared with placebo controls.
Similarly, a "clinically meaningful" improvement from baseline in pain scores was detected as early as 8 weeks following initiation of treatment with ribociclib, and the improvement was sustained over time.
"Longer follow-up is needed to determine whether the trial will meet its secondary endpoint of overall survival," Dr Tripathy noted.
"However, MONALEESA-7 is the first trial to show that ribociclib can be safely and effectively combined with either tamoxifen or a nonsteroidal aromatase inhibitor together with ovarian suppression using goserelin," he added.
Standard of Care
Asked by Medscape Medical News if the MONALEESA-7 study confirms that ribociclib plus endocrine therapy should become the standard of care for this patient population, conference moderator Virginia Kaklamani, MD, professor of medicine, UT Health Science Center, San Antonio, Texas, said that it already is, in her opinion.
"It's very simple," she said. "We have enough data from the other trials to show that once you give this drug along with endocrine therapy — even in premenopausal women that you are making postmenopausal by using goserelin therapy — it is going to work," Dr Kaklamani explained.
"So the concept is there — I am making a young woman postmenopausal by giving her goserelin and then I'm going to give her endocrine therapy on top of that to see if I can benefit her even more — so now we have a large trial in premenopausal women and since these drugs are already approved [in the postmenopausal setting], I'll be using them on every single patient I have that has first-line metastatic breast cancer," she said.
The study was funded by Novartis.
Dr Tripathy declares that Novartis has paid for him to serve on steering committees, consulting fees, and research fees to his institution. Dr Kaklamani has disclosed no relevant financial relationships .
San Antonio Breast Cancer Symposium (SABCS) 2017: Abstract: GS2-05. Presented December 6, 2017.
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Cite this: Ribociclib Effective in Younger Breast Cancer Patients Too - Medscape - Dec 07, 2017.