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Efficacy of Ribociclib Plus Endocrine Therapy vs Combination Chemotherapy in Premenopausal Women With Clinically Aggressive HR+/HER2− Advanced Breast Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowPURPOSE
A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
PATIENTS AND METHODS
In this open-label, multi-center, randomized phase 2 trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomized 1:1 to first-line ribociclib (600 mg daily; 3-weeks-on, 1-week-off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary endpoint was progression-free survival (PFS).
RESULTS
Among 222 patients randomized to ribociclib plus ET (n=112) or combination CT (n=110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic non-visceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. Median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; 95% CI, 17.4-26.7 months) and 12.8 months (combination CT; 95% CI, 10.1-18.4 months); hazard ratio [HR], 0.61; 95% CI, 0.43-0.87; P=.003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (HR, 0.76; 95% CI, 0.55-1.06). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm.
CONCLUSIONS
First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.
Additional Info
Disclosure statements are available on the authors' profiles:
Final results of RIGHT Choice: Ribociclib plus endocrine therapy vs combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2- advanced breast cancer
J. Clin. Oncol 2024 May 21;[EPub Ahead of Print], YS Lu, EI Bin Mohd Mahidin, H Azim, Y Eralp, YS Yap, SA Im, J Rihani, E Gokmen, A El Bastawisy, N Karadurmus, YN Lim, CS Lim, LT Duc, WP Chung, KG Babu, K Penkov, J Bowles, TD Alfaro, J Wu, M Gao, K Slimane, NS El SaghirFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The availability of CDK4/6 inhibitors has dramatically improved outcomes in patients with HR+/HER2− metastatic breast cancer, and, now, these agents (in combination with endocrine therapy) represent the gold standard for first-line treatment of this patient population. However, for patients who have significant visceral disease and require a rapid response, the traditional approach has been to rely on chemotherapy. Moreover, this is the situation where combination chemotherapy is usually employed.
Remarkably, the investigators in this trial challenged this approach and were successful in demonstrating improved progression-free survival outcomes, comparable response rates, and lower rates of symptomatic adverse events with ribociclib plus endocrine therapy versus combination chemotherapy in patients with aggressive HR+/HER2− metastatic breast cancer. This is an extremely important trial, as it challenges the widespread belief that chemotherapy is needed in these situations. Unfortunately, the eventual use of chemotherapy is, in most cases, invariably implemented, and further novel strategies are under investigation to "kick the can" — that is, chemotherapy — "further down the road."