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IMPORTANCE Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. OBJECTIVE To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. DESIGN, SETTING, AND PARTICIPANTS Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. INTERVENTIONS Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). MAIN OUTCOMES AND MEASURES The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. RESULTS Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, −1.34% [95% CI, −2.57% to −0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, −0.55% [95% CI, −1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, −1.13% [95% CI, −1.84% to −0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). CONCLUSIONS AND RELEVANCE Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations.

CARASIL is associated with mutations in the HTRA1 gene. Our findings indicate a link between repressed inhibition of signaling by the TGF-beta family and ischemic cerebral small-vessel disease, alopecia, and spondylosis.

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Purpose Approximately 1% to 2% of non-small-cell lung cancers (NSCLCs) harbor a c-ros oncogene 1 ( ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a small expansion cohort of patients with ROS1-positive advanced NSCLC from an ongoing phase I study. We assessed the efficacy and safety of crizotinib in the largest cohort of patients with ROS1-positive advanced NSCLC. Patients and Methods This phase II, open-label, single-arm trial enrolled East Asian patients with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics, Xiamen, China] at three regional laboratories) advanced NSCLC who had received three or fewer lines of prior systemic therapies. Patients were to receive oral crizotinib at a starting dose of 250 mg twice daily and continued treatment until Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1-defined progression (by independent radiology review [IRR]), unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) by IRR. Results In the efficacy and safety analyses, 127 patients were included, with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95% CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs were similar irrespective of the number of prior lines of therapy, and responses were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to not reached). Median progression-free survival by IRR was 15.9 months (95% CI, 12.9 to 24.0 months). No new safety signals associated with crizotinib were reported. Conclusion This study demonstrated clinically meaningful benefit and durable responses with crizotinib in East Asian patients with ROS1-positive advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile consistent with previous reports.

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Purpose: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard firstline chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM. Patients and Methods: Japanese patients with unresectable, advanced, or metastatic MPM resistant or intolerant to 2 regimens of chemotherapy and 1 measurable lesion (s) were enrolled. Patients received nivolumab 240 mg intravenously every 2 weeks until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate by central assessment according to the Modified Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) and treatment-related AEs (TRAEs) were evaluated. Results: Thirty-four patients were enrolled between July 2016 and October 2016. Median follow-up was 16.8 (range: 1.8-20.2) months. Ten (29%, 95% confidence interval, 16.8-46.2) patients showed a centrally assessed objective response. The objective response rates were 26% (7/27), 67% (2/3), and 25% (1/4) patients for epithelioid, sarcomatoid, and biphasic histologic subtypes, respectively. Median duration of response was 11.1 months with a 68% disease control rate. Median overall survival and progression-free survival were 17.3 and 6.1 months, respectively. The objective response rate was 40% with programmed death-ligand 1 expression 1% and 8% with <1%. Thirty-two patients (94%) experienced AEs and 26 (76%) experienced TRAEs. Conclusions: Nivolumab met the primary endpoint as second-or third-line treatment for patients with MPM and showed promising efficacy with manageable toxicity. See related commentary by Mansfield and Zauderer, p. 5438