Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Induction of cell cycle arrest and apoptosis by grape seed procyanidin extract in human bladder cancer BIU87 cells.

OBJECTIVE: The aim of this study was to evaluate the effects of grape seed procyanidin extract (GSPE) on cell proliferation and apoptosis in human bladder cancer BIU87 cells and to investigate its molecular mechanism in vitro. MATERIALS AND METHODS: BIU87 cells were treated with different concentrations of GSPE for 24h in vitro while an untreated group was taken as control. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, Hoechst 33258 staining, flow cytometry, RT-PCR and Western blot were used to detect the anti-proliferation and apoptotic induction effects of GSPE on BIU87 cells. RESULTS: It was found that GSPE inhibited the cell growth through cell cycle arrest at G1 phase and induced cell apoptosis in BIU87 cells in a dose-dependent manner. Semi-quantitated RT-PCR and Western blot analyses indicated that GSPE increased caspase-3 (p<0.01), but decreased the expression of cyclinD1, CDK4 and survivin (p<0.01). CONCLUSIONS: GSPE inhibits cell proliferation by inducing cell cycle arrest and apoptosis in BIU87 cells, and the effect may be related with its down-regulation of cyclinD1, CDK4 and survivin.