SAN ANTONIO – Results of a study being hailed as practice changing showed that, for pre- or perimenopausal women with aggressive hormone receptor-positive, HER2-negative (HR+/HER2–) untreated breast cancers,
That’s according to investigators of the phase 2 RIGHT Choice study who found that first-line ribociclib, combined with either letrozole or anastrozole plus goserelin, was associated with a doubling of progression-free survival (PFS), compared with the investigator’s choice of combination chemotherapy, reported Yen-Shen Lu, MD, from National Taiwan University Hospital in Taipei, at the San Antonio Breast Cancer Symposium.
“These results from RIGHT Choice have now shown that first-line ribociclib plus endocrine therapy should be considered the preferred treatment option for this patient population,” he said.
Chemo loses its luster
“This is not time first time that we’ve looked at a CDK4/6 inhibitor compared to chemotherapy, but this is the first time that we’ve seen it compared to a combination chemotherapy,” commented Virginia Kaklamani, MD, from University of Texas Health, San Antonio, who moderated a media briefing held prior to Dr. Lu’s presentation of the data in an oral abstract session.
Dr. Virginia Kaklamani
“I think with this study we’re finding that chemotherapy, at least in the early stages of [estrogen receptor]–positive breast cancer, is probably not appropriate for our patients,” she said.
Chemotherapy is the current standard of care for patients with advanced breast cancers with aggressive disease features that can include rapidly progressive disease, high symptom burden, and/or life-threatening visceral crises requiring rapid control of disease, Dr. Lu said.
Compared with single-agent chemotherapy, combination chemotherapy, for those who can tolerate it, is associated with higher overall response rates and longer PFS.
Although ribociclib plus endocrine therapy has been shown to offer significant PFS and overall survival (OS) benefits, compared with endocrine therapy alone, there have not been any head-to-head studies pitting these agents against combination chemotherapy.
Study details
To rectify this, Dr. Lu and colleagues enrolled 222 pre- or perimenopausal women with HR+/HER2– advanced breast cancers with aggressive features who had not yet received systemic therapy for advanced breast cancer.
After stratification for the presence or absence of liver metastases and by length of disease-free interval (time from complete resection of a primary tumor to documented recurrence), the patients were randomly assigned to receive either ribociclib 600 mg 3 weeks on, 1 week off) plus letrozole or anastrozole and goserelin, or the investigators choice of either docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine.
After a median follow-up of 24.1 months at the time of data cutoff in April 2022, median PFS, the primary endpoint, was 24 months in the ribociclib plus endocrine therapy arm versus 12.3 months in the chemotherapy arm.
This translated into a hazard ratio for progression on ribociclib plus endocrine therapy of 0.54 (P = .0007).
The benefit for the ribociclib combination, compared with combination chemotherapy, was consistent across most patient subgroups, Dr. Lu said.
The median time to treatment failure was also longer with ribociclib, at 18.6 months versus 8.5 months, respectively, translating into a HR of 0.45 favoring ribociclib, with a statistically significant confidence interval.
Overall response rates were similar between the groups, at 65.2% with ribociclib versus 60% with chemotherapy. The respective clinical benefit rates (including complete and partial responses plus stable disease) were 80.4% versus 72.7%.
The time to response was similar between the treatment arms, an important consideration for patients with rapidly progressive disease, Dr. Lu noted.
Adverse events that occurred more frequently with ribociclib were neutropenia and leukopenia. Events more common with chemotherapy included anemia, liver enzyme elevations, nausea, vomiting, diarrhea, alopecia, fatigue, and palmar-plantar erythrodysesthesia.