BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion

Purpose: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO). Design: Two identically designed global, randomized, double-masked, active comparator–controlled studies. Participants: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO. Methods: Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend–based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA). Main Outcome Measures: Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0–24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of ≥ 15/≥ 10/≥ 5/> 0 letters. Secondary end points (weeks 24–72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed. Results: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers). Conclusions: Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

The current evidence on statin use and prostate cancer prevention: are we there yet?

An increasing amount of data supports an inverse association between statin use and cancer risk. The findings for prostate cancer, particularly advanced disease, are the most promising of all cancers studied. Use of these agents seems to also be associated with improved prostate-cancer-specific survival, particularly in men undergoing radiotherapy, suggesting usefulness of statins in secondary and tertiary prevention. Some study results might be influenced by increased PSA screening and health-conscious behaviour in statin users but these factors are unlikely to completely account for observed beneficial effects. The epidemiological evidence is supported by preclinical studies that show that statins directly inhibit prostate cancer development and progression in cell-based and animal-based models. The antineoplastic effect of statins might arise from a number of cholesterol-mediated and non-cholesterol-mediated mechanisms that affect pathways essential for cancer formation and progression. Understanding these mechanisms is instrumental in drug discovery research for the development of future prostate cancer therapeutics, as well as in designing clinical trials to test a role for statins in prostate cancer prevention. Currently, sufficient data are lacking to support the use of statins for the primary prevention of prostate cancer and further research is clearly warranted. Secondary and tertiary prevention trials in men who have been diagnosed with prostate cancer might soon be performed