SAN ANTONIO – The inhibitor of CDK4 / 6 ribociclib ( Kisqali Novartis) dramatically improves progression-free survival (PFS) when added to endocrine therapy in younger patients with positive hormone receptors suppressed (HR +), advanced breast cancer 2 negative receptor of the human epidermis (HER2-), according to the first data of its kind.
In summary, it is beneficial to add the medication to what is a first-line treatment established for pre-and perimenopausal women with this type of breast cancer.
"MONALEESA-7 is the first clinical trial that has the statistical power to demonstrate that ribociclib has a clinical benefit specifically for pre and perimenopausal women," Debu Tripathy, MD, professor of medicine and chairman of the department of medical oncology at Mom at the MD Anderson Cancer Center at the University of Texas at Houston, said in a statement.
Ribociclib is "a potentially important treatment option for premenopausal patients with this type of treatment". advanced breast cancer, "he added at a press conference.
The study was reported here at the San Antonio Breast Cancer Symposium (SABCS) 2017.
In the MONALEESA-2 trial, the researchers demonstrated that the addition of ribociclib at the first prolonged endocrine PFS in line in postmenopausal women with HR +, HER2-advanced disease.
In the new phase 3 trial, Dr. Tripathy and coinvestigators randomized 335 women to endocrine therapy and ribociclib, and 337 women on 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 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, "said Dr. Tripathy.
The median follow-up at the cut-off point of the trial was 19.2 months.
At follow-up, the median PFS in the endocrine and ribociclib therapy group was 23.8 months compared to 13.0 months for the control group, suggesting that treatment with the additional CDK4 / 6 inhibitor reduced the risk of progression by half (instantaneous hazard ratio, 0.55; P <.001).
of the endocrine therapy received by the patients also appeared to have no effect on the rate of superior SSP in the ribociclib arm.
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 performed by a blind independent review committee, the median PFS had not been reached at trial cut-off in patients receiving ribociclib compared to a median SSE of 11.1 months for The 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. " , observed Dr. Tripathy.
There were also significant differences in the secondary endpoint of the overall response rate (40.9% in the ribociclib arm versus 29.7% in the placebo arm).
Many were produced more interruptions in the dose in the CDK4 / 6 inhibitor arm, mainly due to adverse events (AEs). Approximately one third of the patients in the ribociclib group also They required a reduction in the dose.
Grade 3 and 4 neutropenia was the most frequent haematological EA that was observed in association with the CDK4 / 6 inhibitor, in approximately 60% of patients the ribociclib arm. Febrile neutropenia was rare and occurred only in approximately 2% of patients.
Rates of non-haematological toxicities were similar in both treatment groups; the most frequent were hot flushes and arthralgias, probably related to the use of tamoxifen or an aromatase inhibitor.
Interruption rates due to AD were similar in both groups, approximately 3%.
It is important to note that the quality reported by the patients' life results reflecting the overall health status showed that there was a sustained improvement over time until the definitive deterioration in the ribociclib arm compared to the placebo controls.
Similarly, a "clinically significant" improvement was detected from the beginning in the pain scores 8 weeks after the start of ribociclib treatment, and the improvement was maintained over time.
"A longer follow-up is needed to determine if the trial will reach its secondary endpoint of overall survival," Dr. Tripathy said.
However, MONALEESA-7 is the first test that shows that ribociclib can be safely and effectively combined with tamoxifen or a non-steroidal aromatase inhibitor along with ovarian suppression using goserelin. "
] Standard of care
Asked by Medscape Medical News if the MONALEESA-7 study confirms that treatment with more endocrine ribociclib should become the standard of care for this patient population, the moderator of the conference Virginia Kaklamani, MD, professor of medicine, UT Health Science Center, San Antonio, Texas, said she already is, in her opinion.
"It's very simple," she said. "We have enough data from the other trials to demonstrate that once this medication is given along with endocrine therapy, even in premenopausal women who are undergoing postmenopause through the use of goserelin therapy, it will work " explained Dr. Kaklamani.
"So the concept is there: I'll do a post-menopause to a young woman giving her goserelin and then I'll give her an endocrine therapy to see if I can benefit her even more, so now we have a big test." in premenopausal women and since these medications are already approved [in the postmenopausal setting] I will use them in every patient that I have that has metastatic breast cancer first line, "he said.
The study was funded by Novartis.
Dr. Tripathy states that Novartis has paid him to serve on management committees, consulting fees and research fees to his institution, Dr. Kaklamani has not disclosed any relevant financial relationship . ]
San Antonio Breast Cancer Symposium (SABCS) 2017: Summary: GS2-05.Submitted on December 6, 2017.
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