According to findings from the phase II RIGHT Choice trial, many premenopausal patients with metastatic hormone receptor–positive, HER2-negative breast cancer experiencing visceral crisis are best treated with first-line ribociclib plus endocrine therapy rather than with chemotherapy.¹

Ribociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), given with endocrine therapy, led to a doubling in median progression-free survival compared with combination chemotherapy and was associated with fewer adverse events, according to Yen-Shen Lu, MD, PhD, Professor and Division Chief of Medical Oncology at National Taiwan University Hospital in Taipei. Dr. Lu presented the findings at the 2022 San Antonio Breast Cancer Symposium. 

Yen-Shen Lu, MD, PhD

“The results of the RIGHT Choice trial reveal that front-line ribociclib plus endocrine therapy can be an efficacious, clinically meaningful treatment option for patients with aggressive advanced breast cancer and helps to avoid the need for combination chemotherapy and its associated toxicities,” Dr. Lu said.

As Dr. Lu noted, the combination of CDK4/6 inhibitors plus endocrine therapy has been widely adopted as first-line treatment in hormone receptor–positive, HER2-negative metastatic breast cancer. However, many guidelines continue to recommend chemotherapy for the subset with rapidly progressing or highly symptomatic disease. The RIGHT Choice trial challenges that recommendation.

Moderator of a press briefing, Virginia Kaklamani, MD, SABCS Co-Director and Professor of Medicine at UT Health San Antonio, said the study is the first to compare a CDK4/6 inhibitor with combination chemotherapy. “I agree that these findings will change some of the standard of care,” she said. “We don’t use a lot of chemotherapy nowadays because of how well the CDK4/6 inhibitors work, but I think the little that we use is probably now dead.” 

Virginia Kaklamani, MD

Ruth O’Regan, MD

Also at the press briefing, Ruth O’Regan, MD, Professor and Chairman of Medicine at the University of Rochester in New York, commended the investigators of the study. “I think this is a question we’ve had, and even though this is a phase II study, it is really showing us that we don’t need to use chemotherapy for these patients.”

RIGHT Choice Details

The trial enrolled 222 pre- or perimenopausal women with hormone receptor–positive, HER2-negative previously untreated aggressive breast cancer. More than half (52%) were determined to be in visceral crisis, as indicated by rapidly progressing disease or impending visceral compromise, symptomatic visceral metastases, or markedly symptomatic nonvisceral disease. The population was 54% Asian and 46% White. 

Patients were randomly assigned to receive ribociclib at 600 mg for 3 weeks on, 1 week off, given with letrozole or anastrozole plus goserelin or investigator’s choice of combination chemotherapy, which could be docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine. Patients were followed for a median of 24 months. The primary endpoint was progression-free survival by local assessment. At the time of data cutoff, 46% of patients were continuing ribociclib compared with 24% continuing combination chemotherapy. 

Doubling in Progression-Free Survival

“There was a significant progression-free survival benefit of 1 additional year [with ribociclib] compared with combination chemotherapy. The benefit was consistent for most subgroups of patients,” Dr. Lu reported. 

Median progression-free survival was 24.0 months with ribociclib plus endocrine therapy compared with 12.3 months with combination chemotherapy (hazard ratio [HR] = 0.54; P = .0007). Overall response rate was 65.2% for ribociclib plus endocrine therapy compared with 60.0% for combination chemotherapy, and the time to response was rapid and similar: 4.9 months and 3.2 months, respectively (HR = 0.78).

“Combination chemotherapy is known to have a high response rate, which is why it is sometimes preferred for this patient group. In both arms, the overall response rate was similar,” he said. “Ribociclib plus endocrine therapy can generate a high tumor response rate, matching the data with combination chemotherapy.” 

Tolerability

Tolerability was better with ribociclib plus endocrine therapy than with combination chemotherapy, with serious treatment-related adverse events seen in 1.8% and 8.0%, respectively, and treatment-related discontinuations reported in 7.1% and 23.0%, respectively. Although neutropenia and leukopenia were more common with ribociclib plus endocrine therapy, chemotherapy-treated patients were much more likely to report nausea, vomiting, and diarrhea—“which impact quality of life,” Dr. Lu noted.  

“Younger patients with aggressive disease often show resistance to treatment, resulting in worse prognoses. So, it is encouraging to see RIGHT Choice data demonstrating a significant 1-year benefit for this patient population with ribociclib plus endocrine therapy,” he concluded. 

DISCLOSURE: Dr. Lu has served as an advisor to or speaker for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Europharma, Merck Sharp & Dohme, Novartis, and Roche. Dr. Kaklamani has served as a consultant to or a speaker for Puma, AstraZeneca, Daiichi Sankyo, Menarini, Gilead Sciences, Pfizer, Genentech, Exact Sciences, Novartis, and Seagen and has received research support from Eisai. Dr. O’Regan reported no conflicts of interest.

REFERENCE

1. Lu YS, Bin Mohd Mahidin EI, Azim H, et al: Primary results from the randomized phase II RIGHT Choice trial of premenopausal patients with aggressive hormone receptor–positive HER2-negative advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy. 2022 San Antonio Breast Cancer Symposium. Abstract GS1-10. Presented December 6, 2022.