Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

Comparison of running performances and prevalence of overweight and obesity in Hungarian and Ukrainian adolescents

The 20-m shuttle run (20-mSRT) is a widely used field test to estimate peak oxygen consumption (VO2peak) and thus to assess aerobic fitness of adolescents (11). The purpose of this study was to analyse differences in basic anthropometric measurements (stature, body mass, percent body fat, BMI) and in aerobic fitness of Hungarian and Ukrainian adolescent boys and girls. We examined gender differences in maximal speed (km h−1), in peak VO2 (mL kg−1 min−1) and maximal heart rate (HRmax min−1). Two hundred ninety-two Ukrainian (mean age=16.5±0.5) and 374 (mean age=16.5±0.5) Hungarian adolescents volunteered to participate in this study. Differences were analysed using factorial analysis of the variance (ANOVA) and Student’s t-test. Statistical significance was set at p<0.05. Hungarian boys and girls were significantly taller, heavier and had higher percent body fat than their Ukrainian counterparts. Altogether 10% of Hungarians and 7% of Ukrainians were classified overweight or obese according to Cole’s BMI classification (4). VO2peak of Ukrainians (mean=49.44±5.29 mL kg−1 min−1) were significantly higher than that of Hungarians (mean=41.93±8.40 mL kg−1 min−1). Maximal heart rate also differed significantly (Ukrainians mean=201.12±8.43 min−1 vs. Hungarians mean=185.38±18.38 min−1).In conclusion, aerobic fitness of the Ukrainian adolescents was significantly higher than that of the Hungarians independently of BMI or gender