Patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, including those with visceral crises, treated with the CDK4/6 inhibitor ribociclib (Kisqali) plus endocrine therapy had a significantly longer progression-free survival (PFS) and fewer adverse events (AEs) compared with those treated with combination chemotherapy, according to results from the phase 2 RIGHT Choice trial.
“These findings suggest that, through the use of first-line ribociclib plus endocrine therapy, we may be able to avoid or delay chemotherapy and spare patients—even those with aggressive, life-threatening disease—the toxicities and discontinuations associated with chemotherapy,” said Yen-Shen Lu, MD, PhD, Division Chief, Medical Oncology, and Clinical Associate Professor, Internal Medicine, National Taiwan University College of Medicine, Taipei, while discussing the results of this study during the 2022 San Antonio Breast Cancer Symposium.
“Practice Changing” Results
Dr Lu said that these findings are “practice changing,” given that chemotherapy has been the preferred initial treatment for patients with HR-positive, HER2-negative advanced breast cancer with aggressive characteristics, such as visceral crisis. More than 50% of patients in the study had visceral crisis, defined as the presence of metastases that compromise function of vital organs.
Physicians may be hesitant to move away from combination chemotherapy in this population because of the rapid tumor response, he noted, but the data from RIGHT Choice endorse the choice of ribociclib plus endocrine therapy. In this trial, time to response was not significantly different between the ribociclib plus endocrine therapy and chemotherapy arms (4.9 vs 3.2 months, respectively).
The RIGHT Choice study included 222 premenopausal or perimenopausal patients with aggressive, HR-positive, HER2-negative advanced breast cancer. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib (600 mg daily, 3 weeks on/1 week off) plus an aromatase inhibitor (letrozole [Femara] or anastrozole [Arimidex]) and goserelin (Zoladex) or physician’s choice of combination chemotherapy (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine).
Aggressive disease was defined as the presence of symptomatic visceral metastases, rapid disease progression or impending visceral compromise, or markedly symptomatic nonvisceral disease. Eligible patients could not have received previous systemic therapy for advanced breast cancer.
Patients randomized to receive ribociclib plus endocrine therapy had a median PFS of 24 months, which was nearly 1 year longer than the median PFS in patients who received combination chemotherapy (12.3 months). The median time to treatment failure was also prolonged in the ribociclib plus endocrine therapy arm compared with the combination chemotherapy arm (18.6 months vs 8.5 months, respectively). The overall response rate was similar between the 2 treatment arms (65% in the CDK4/6 inhibitor arm vs 60% in the combination chemotherapy arm).
Treatment is ongoing in 45.5% and 23.6% of patients in the ribociclib plus endocrine therapy and combination chemotherapy arms, respectively. Disease progression was the reason for treatment discontinuation in 44.6% of patients in the ribociclib plus endocrine therapy arm versus 52.7% of the combination chemotherapy arm. The median duration of treatment exposure was 15.0 months and 8.6 months, respectively.
Tolerability was superior with the CDK4/6 combination. Serious treatment-related AEs (TRAEs) occurred in 1.8% of patients receiving ribociclib plus endocrine therapy and in 8% of those receiving combination chemotherapy, and 7.1% versus 23%, respectively, discontinued at least one component of study treatment due to TRAEs.
“Compared with combination chemotherapy, ribociclib plus endocrine therapy may offer more durable antitumor efficacy with better tolerability and compliance,” Dr Lu said. “Overall, these improvements in outcomes and tolerability should translate into an evolution of our standard of care for patients with hard-to-treat breast cancer, providing clinicians with guidance for treating this patient population.”
These data will probably lead to an abandonment of chemotherapy for this indication, said Virginia Kaklamani, MD, DSc, Ruth McLean Bowman Bowers Chair in Breast Cancer Research and Treatment; A.B. Alexander Distinguished Chair in Oncology; and Leader, Breast Cancer Program, University of Texas Health San Antonio MD Anderson Cancer Center. “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,” based on these results, she added.