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
Mené sur 542 patients atteints d'un cancer urothélial de stade avancé et récidivant, cet essai de phase III compare l'efficacité, du point de vue de la survie globale et de la survie sans progression, et la toxicité du pembrolizumab et d'une chimiothérapie choisie par le médecin (paclitaxel, docétaxel ou vinflunine) après l'échec d'un traitement de première ligne à base de sels de platine (durée médiane de suivi : 27,7 mois)
Background : Novel 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 Methods : Adult 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. Results : A total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n =272). Median follow-up as of October 26, 2017, was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) then 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% vs 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% vs 90.6%) and grade ≥3 (16.5% vs 50.2%) treatment-related adverse events than chemotherapy. Conclusions : Long-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.
Annals of Oncology 2019