Remimazolam tosilate (RT) is a new short-acting γ-aminobutyric acid A (GABAA) receptors agonist. However, its optimal use mode and dosage still remain unclear. This study aimed to examine the safety and effectiveness of the combination of RT and propofol in gastroscopy. This was a prospective, single-blind, randomized, multicenter, parallel-group study. All eligible 256 patients were randomized into the following 3 groups. Patients were anesthetized with propofol (Group P), RT (Group R) or the combination of RT and propofol (Group RP). The primary efficacy endpoints were: body movement score; satisfaction of gastroscopy doctors; success rate of sedation and effects on sleep status. Sedation induction time, time to be fully alert and adverse events were also recorded. The probability of complete immobility was lower in group R (33.73%) than in group P (86.67%) and RP (83.13%). The rate of doctors’ satisfaction was much lower in group R (28.92%) than in group P (77.78%) and RP (72.29%). The success rate of sedation and sleep outcome score has no difference in the three groups. The time to adequate sedation was longer in group RP (77.27 ± 18.63 s) than in group P (64.47 ± 24.36 s), but much shorter than that in group R (102.84 ± 46.43s). The time to be fully alert was shorter in group R (6.30 ± 1.52 min) and RP (6.54 ± 1.13 min) than in group P (7.87 ± 1.08 min). The proportion of sedative hypotension was significantly higher in group P (41.11%) than in group R (1.20%) and group RP (3.61%) (p < 0.001). The incidence of respiratory depression was much higher in group P (17.78%) than in group R (no patient) and group RP (1.2%). The incidence of adverse events was lower in groups R (4.82%) and RP (9.64%) than in group P (31.11%). The combination of RT and propofol takes effect quickly, makes patients alert quickly, provides a sufficient depth of sedation, reduces body movement, does not inhibit circulation and respiratory function, does not affect sleep, and is the preferred mode for gastroscopy doctors and anesthesiologists.
Background: Multicenter studies have shown improved clinical outcomes and favorable safety with pembrolizumab (pembro) in 1L and 2L settings in advanced NSCLC. We present pembro data in Chinese patients (pts) with advanced NSCLC. Method: This open label phase 1 study (NCT02835690) enrolled Chinese pts aged 18 years with histologically/cytologically confirmed advanced, unresectable NSCLC; measurable disease per RECIST v1.1; ECOG PS 0/1; and prior failure/ intolerance/ineligibility for standard therapy. Pts were randomized (stratified by gender) 1:1:1 to IV pembro 2 mg/kg, 10 mg/kg, or 200 mg (each Q3W after initial 28-day cycle). Safety and PK were primary objectives. Responses were assessed centrally per RECIST v1.1. PK was based on noncompartmental analysis. Result: 42 pts received 1 pembro dose (2 pts randomized were not treated thus excluded from analyses; 2 mg/kg, n ¼ 14; 10 mg/kg, n ¼ 13; 200 mg, n ¼ 15): median age 59 (range, 28e71) y, 64% male, 62% adenocarcinoma, and 76% 1e2 prior therapies. Median follow up was 7.9 mo (range, 0.7e13.1). 29 pts (69%) had treatment-related AEs, most commonly fatigue and rash (24% each). 4 pts (10%) had grade 3-4 treatment-related AEs (no grade 5): eyelid ptosis, fatigue, anaphylactic reaction, dermatitis acneiform, and rash (1 each). AEOSIs (predefined list with possible immune etiology) were hypothyroidism (n ¼ 2) and hyperthyroidism, anaphylactic reaction, and rash (n ¼ 1 each). Geometric mean PK values for 2 mg/kg, 10 mg/kg, and 200 mg, respectively, were: t 1/2 (days; CV %), 15 (33), 16 (25), and 12 (41); AUC 0-21d (mg$d/mL; 95% CI), 730.9 (627.4e851.6), 2819.2 (2009.4e3955.4), and 931.0 (724.4e1196.6); and C max (mg/mL; 95% CI), 66.7 (56.9e78.1), 268.6 (217.8e331.2), and 92.2 (81.7e104.2). Anti-drug antibodies did not impact pembro exposure. Overall, ORR was 14.3% (6/42; 95% CI, 5.4e28.5); median DOR was 5.2 mo (range, 2.00 [ongoing]e6.28), PFS was 2.1 mo (range, 2.1e4.2), and OS was not reached. Conclusion: In Chinese pts with advanced NSCLC, pembro had approximately linear serum exposure at the dose range studied (2 to 10 mg/kg), was well tolerated, and showed antitumor activity consistent with the multicohort study KEYNOTE-001. The phase 3 KEYNOTE-033 study (NCT02864394), enrolling mostly Chinese pts, evaluates pembrolizumab versus docetaxel in pts with previously treated NSCLC with PD-L1 TPS 1% and is ongoing.
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