Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer.

BACKGROUND: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. METHODS: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. RESULTS: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab-. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3-12.9] vs 3.1 [1.9-5.3] months, hazard ratio, 0.38 [0.22-0.66]; P = 0.0006; Tmab-, 4.8 [4.1-6.0] vs 4.2 [3.6-4.9] months, 0.71 [0.57-0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5-4.0] vs 1.5 [1.3-2.9] months, 0.49 [0.29-0.85]; P = 0.0111; Tmab-, 1.6 [1.5-2.4] vs 1.5 [1.5-1.5] months, 0.64 [0.51-0.80]; P = 0.0001). CONCLUSIONS: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

A randomized, double-blind, placebo-controlled, phase III study of the short-acting ß1-adrenergic receptor blocker landiolol hydrochloride for coronary computed tomography angiography in Japanese patients with suspected ischemic cardiac disease.

OBJECTIVES AND BACKGROUND: The objective of this study was to investigate the image quality-improving and heart rate-lowering effects of landiolol hydrochloride (a short-acting ß1-adrenergic receptor blocker) on coronary computed tomography angiography (CCTA). During CCTA, ß-adrenergic receptor blockers have been commonly used to lower heart rate and improve image quality. METHODS: A total of 258 subjects suspected of having ischemic cardiac disease and requiring CCTA were randomized to either a landiolol hydrochloride 0.125 mg/kg group or placebo group to study the efficacy and safety of landiolol hydrochloride in a multicenter, double-blind, randomized parallel study. The primary endpoint was the diagnosable proportion (proportion of subjects whose coronary stenosis was diagnosable). RESULTS: The diagnosable proportions about the reconstruction images at mid-diastole were 68.2 and 38.2 % in the landiolol hydrochloride and placebo group, respectively, indicating significant superiority of landiolol hydrochloride over placebo (p < 0.0001). The diagnosable proportions about the optimal reconstruction images were 81.4 and 54.2 % in the landiolol hydrochloride and placebo group, respectively, indicating significant superiority of landiolol hydrochloride over placebo (p < 0.0001). The mean heart rate-lowering effect was first observed soon after administration of landiolol hydrochloride, was most marked at 3-5 min, and disappeared 30 min after completion of administration. The mean heart rate-lowering proportion at that time was -19.1 ± 8.1 % and -5.9 ± 9.7 % in the landiolol hydrochloride and placebo groups, respectively, showing a significantly higher proportion in the landiolol hydrochloride group. CONCLUSIONS: Landiolol hydrochloride was confirmed to significantly and rapidly lower heart rate after intravenous injection, suggesting that it is a safe and useful agent for improving the image quality of CCTA.

A multicenter, open-label study of an intravenous short-acting ß1-adrenergic receptor antagonist landiolol hydrochloride for coronary computed tomography angiography by 16-slice multi-detector computed tomography in Japanese patients with suspected ischemic cardiac disease.

BACKGROUND: During coronary computed tomography (CT) angiography (CCTA), ß-blockers (ß-adrenergic receptor antagonists) have commonly been used to lower heart rate and improve image quality. OBJECTIVES: The aim of this study was to investigate the image quality-improving effect as well as the heart rate-lowering effect of landiolol hydrochloride (an intravenous short-acting ß1-adrenergic receptor antagonist) in CCTA by 16-slice multi-detector CT (MDCT). METHODS: A total of 39 subjects suspected of having ischemic cardiac disease and requiring CCTA received 0.125 mg/kg of landiolol hydrochloride to study the efficacy and safety of landiolol hydrochloride in a multicenter open-label clinical study. The endpoint was the diagnosable proportion (proportion of subjects whose coronary stenosis was diagnosable). RESULTS: The diagnosable proportions for the reconstruction images at mid-diastole were 56.0 %. The diagnosable proportions for the optimal reconstruction images were 65.4 %. The mean heart rate-lowering effect was observed soon after administration of landiolol hydrochloride; the peak of the effect was reached in 3-5 min, and the effect wore off in 30 min after completion of administration. The mean heart rate-lowering proportion at that time was -14.46 ± 8.4 %. CONCLUSIONS: Landiolol hydrochloride was confirmed to reduce heart rate significantly and rapidly after intravenous injection and this suggests that the study drug is a safe and useful agent for improving the image quality of CCTA by 16-slice MDCT.