Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

PURPOSE: 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). METHODS: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once 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 end point was progression-free survival (PFS). RESULTS: Among 222 patients randomly assigned 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 nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The 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 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 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 (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. CONCLUSION: 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.

Synergistic effect of Pt-Ni dual single-atoms and alloy nanoparticles as a high-efficiency electrocatalyst to minimize Pt utilization at cathode in polymer electrolyte membrane fuel cells.

Pt-Ni (111) alloy nanoparticles (NPs) and atomically dispersed Pt have been shown to be the most effective catalysts for oxygen reduction reaction (ORR) in polymer electrolyte membrane fuel cells (PEMFCs) as well as less expensive compared to pure Pt NPs. To meet reaction kinetic demands and minimize the Pt utilization at cathode in PEMFCs, we propose a novel electrocatalyst composed of dual single-atoms (Pt, Ni) and Pt-Ni alloy NPs dispersed on the surface of N-doped carbon (NDC); collectively, PtNiSA-NPS-NDC. The optimized PtNiSA-NPS-NDC catalyst displays excellent mass activity and durability compared to commercial Pt/C. Electrocatalytic measurements show that the PtNiSA-NPS-NDC catalyst, with a metal loading of 4.5 wt%, exhibited distinguished ORR performance (E1/2 = 0.912 V) through a 4-electron (4e-) pathway, which is higher than that of commercial 20 wt% Pt/C (E1/2 = 0.857 V). The DFT simulations indicate Pt-Ni alloy NPs and PtNiN2C4 atomic structure are the mobile active sites for ORR catalytic activity in PtNiSA-NPS-NDC. As a cathode catalyst in PEMFC, the Pt utilization efficiency in the PtNiSA-NPS-NDC catalyst is 0.033 gPt kW-1, which is 5.6 times higher than that of commercial Pt/C (0.185gPt kW-1). Therefore, the consumption of precious metals is effectively minimized.