SAN ANTONIO (FRONTLINE MEDICAL NEWS) – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.

In the randomized phase 3 MONALEESA-7 trial , the first phase 3 study of a cyclin-dependent kinase (CDK) 4/6 inhibitor in premenopausal women with breast cancer, the median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor (AI) or tamoxifen plus the luteinizing, hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo, reported Debu Tripathy, MD , from the University of Texas MD Anderson Cancer Center in Houston.

The hazard ratio for the ribociclib-based combination was 0.553 (P less than .0001), he reported at the San Antonio Breast Cancer Symposium.

“The treatment benefit was seen across all subgroups, and also regardless of the endocrine partner, either tamoxifen or aromastase inhibitors,” he said.

The combination of ribociclib with goserelin and either tamoxifen or a nonsteroidal AI is a potential new treatment option for premenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, regardless of the disease-free interval or the endocrine partner, he said in a media briefing and in an oral session.

In the United States, approximately 19% of invasive breast cancers are diagnosed in women aged 49 years or younger, and in the Asia/Pacific region, the proportion of patients aged younger than 50 years with invasive breast cancer may be as high as 42%, Dr. Tripathy said.

The need for new therapeutic approaches in this population is clear, with the last randomized clinical trial focused solely on women with advanced premenopausal breast being published 17 years ago, he pointed out.

Given the efficacy of adding ribociclib to standard AI therapy in postmenopausal women with advanced HR+/HER2- breast cancer as seen in the MONALEESA-2 trial , the MONALEESA-7 investigators looked at the same combination as first-line therapy in premenopausal women with similar disease features.

In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to the ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.

Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment.

Investigator-assessed progression-free survival was the primary endpoint, as noted before. The findings were supported by an analysis of the data by a blinded independent review committee, which determined the median PFS to not have been reached in the ribociclib arm, compared with 11.1 months in the placebo arm, with a hazard ratio of 0.427, and a 95% confidence interval showing statistical significance.

The secondary endpoint of overall response rate (ORR) was also significantly better with ribociclib among the entire patient population (40.9% vs. 29.7%; P = .00098), and in patients with measurable disease (50.9% vs. 36.4%; P = .000317).

An analysis of PFS by endocrine agent (tamoxifen or AI) showed similar hazard ratios with each class of agent combined with ribociclib.

Hematologic adverse events occurred in 75.8% of all patients on ribociclib, compared with 7.7% of those on placebo. In the CDK4/6 inhibitor arm, 50.7% of patients had grade 3 neutropenia, and 9.9% had grade 4. Febrile neutropenia occurred in 2.1% of patients on ribociclib, compared with 0.6% of patients on placebo.

Nonhematologic adverse events were generally similar between the trial arms, with the exception of more frequent nausea with ribociclib.

Ribociclib also was associated with significantly better patient-reported outcomes, including longer time to deterioration of QoL scores, and better improvement in pain scores from baseline.

Despite the highly encouraging data, the finding is not exactly paradigm changing, because ribociclib already is approved for use in breast cancer, but the trial is important because it represents the largest study to date in premenopausal women, commented Virginia Kaklamani, MD , from the University of Texas Health, in San Antonio, who moderated the briefing.

“For me, I would now be very comfortable giving these women an aromatase inhibitor plus goserelin and riboclicib,” she said in an interview.

SABCS fixture Steven “Vogl, New York” Vogl, MD, a medical oncologist in private practice in New York, commented after Dr. Tripathy’s presentation that, “I think that this is a momentous study, and I think it should immediately change the standard of care for symptomatic young women with metastatic breast cancer. More of them get better, and they stay better longer. These are people who we’re trying to buy some good life for, before the inevitable happens.”

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company. Dr. Kaklamani reported serving as a consultant to Novartis. Dr. Vogl reported no conflicts of interest.