Thomas Powles1, Se Hoon Park1, Eric Voog1, Claudia Caserta1, Begoña P Valderrama1, Howard Gurney1, Haralabos Kalofonos1, Siniša Radulović1, Wim Demey1, Anders Ullén1, Yohann Loriot1, Srikala S Sridhar1, Norihiko Tsuchiya1, Evgeny Kopyltsov1, Cora N Sternberg1, Joaquim Bellmunt1, Jeanny B Aragon-Ching1, Daniel P Petrylak1, Robert Laliberte1, Jing Wang1, Bo Huang1, Craig Davis1, Camilla Fowst1, Nuno Costa1, John A Blake-Haskins1, Alessandra di Pietro1, Petros Grivas1. 1. From Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London (T.P.); Sungkyunkwan University Samsung Medical Center, Seoul, South Korea (S.H.P.); Centre Jean Bernard Clinique Victor Hugo, Le Mans (E.V.), and Gustave Roussy, INSERM Unité 981, Université Paris-Saclay, Villejuif (Y.L.) - both in France; the Medical Oncology Unit, Azienda Ospedaliera S. Maria, Terni (C.C.), and Pfizer, Milan (C.F., A.P.) - both in Italy; the Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Seville, Spain (B.P.V.); the Department of Clinical Medicine, Macquarie University, Sydney (H.G.); the Division of Oncology, Department of Medicine, University General Hospital of Patras, Patras, Greece (H.K.); the Institute for Oncology and Radiology of Serbia, Belgrade (S.R.); the Department of Medical Oncology, Algemeen Ziekenhuis Klina, Brasschaat, Belgium (W.D.); Patient Area Pelvic Cancer, Theme Cancer, Karolinska University Hospital, and the Department of Oncology-Pathology, Karolinska Institute, Solna, Sweden (A.U.); Princess Margaret Cancer Centre, University Health Network, Toronto (S.S.S.); the Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan (N.T.); the State Institution of Healthcare Regional Clinical Oncology Dispensary, Omsk, Russia (E.K.); the Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York (C.N.S.); the Department of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (J.B.), and Pfizer, Cambridge (R.L., J.W.) - both in Massachusetts; Inova Schar Cancer Institute, Fairfax, VA (J.B.A.-C.); Yale Cancer Center, New Haven (D.P.P.), and Pfizer, Groton (B.H.) - both in Connecticut; Pfizer, La Jolla, CA (C.D., J.A.B.-H.); Pfizer, Porto Salvo, Portugal (N.C.); and the Department of Medicine, Division of Oncology, University of Washington, and the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle (P.G.).
Abstract
BACKGROUND: Platinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance. METHODS: In a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety. RESULTS: Among all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = 0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free survival was 3.7 months in the avelumab group and 2.0 months in the control group in the overall population (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group; the incidence of adverse events of grade 3 or higher was 47.4% and 25.2%, respectively. CONCLUSIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).
BACKGROUND: Platinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance. METHODS: In a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety. RESULTS: Among all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = 0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P<0.001). The median progression-free survival was 3.7 months in the avelumab group and 2.0 months in the control group in the overall population (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75) and 5.7 months and 2.1 months, respectively, in the PD-L1-positive population (hazard ratio, 0.56; 95% CI, 0.43 to 0.73). The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group; the incidence of adverse events of grade 3 or higher was 47.4% and 25.2%, respectively. CONCLUSIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Bladder 100 ClinicalTrials.gov number, NCT02603432.).
Authors: Thomas Powles; Jonathan E Rosenberg; Guru P Sonpavde; Yohann Loriot; Ignacio Durán; Jae-Lyun Lee; Nobuaki Matsubara; Christof Vulsteke; Daniel Castellano; Chunzhang Wu; Mary Campbell; Maria Matsangou; Daniel P Petrylak Journal: N Engl J Med Date: 2021-02-12 Impact factor: 91.245
Authors: Risa L Wong; Lorin A Ferris; Olivia A Do; Sarah K Holt; Jorge D Ramos; Simon J Crabb; Cora N Sternberg; Joaquim Bellmunt; Sylvain Ladoire; Ugo De Giorgi; Lauren C Harshman; Ulka N Vaishampayan; Andrea Necchi; Sandy Srinivas; Sumanta K Pal; Guenter Niegisch; Tanya B Dorff; Matthew D Galsky; Evan Y Yu Journal: Oncologist Date: 2021-08-17