Search

Your search keyword '"Fradet, Y"' showing total 725 results
Start Over Author "Fradet, Y"
725 results on '"Fradet, Y"'

2. 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

Author

Fradet, Y, Bellmunt, J, Vaughn, DJ, Lee, JL, Fong, L, Vogelzang, NJ, Climent, MA, Petrylak, DP, Choueiri, TK, Necchi, A, Gerritsen, W, Gurney, H, Quinn, DI, Culine, S, Sternberg, CN, Nam, K, Frenkl, TL, Perini, RF, de Wit, R, and Bajorin, DF

Subjects
Clinical Research, Cancer, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Docetaxel, Follow-Up Studies, Humans, Neoplasm Recurrence, Local, Paclitaxel, Prognosis, Response Evaluation Criteria in Solid Tumors, Survival Rate, Urologic Neoplasms, Vinblastine, PD-L1, PD-1, pembrolizumab, urothelial cancer, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

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.

Published
2019

3. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma:results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up

Author

Balar, A. V., Castellano, D. E., Grivas, P., Vaughn, D. J., Powles, T., Vuky, J., Fradet, Y., Lee, J. L., Fong, L., Vogelzang, N. J., Climent, M. A., Necchi, A., Petrylak, D. P., Plimack, E. R., Xu, J. Z., Imai, K., Moreno, B. H., Bellmunt, J., de Wit, R., O'Donnell, P. H., Balar, A. V., Castellano, D. E., Grivas, P., Vaughn, D. J., Powles, T., Vuky, J., Fradet, Y., Lee, J. L., Fong, L., Vogelzang, N. J., Climent, M. A., Necchi, A., Petrylak, D. P., Plimack, E. R., Xu, J. Z., Imai, K., Moreno, B. H., Bellmunt, J., de Wit, R., and O'Donnell, P. H.

Abstract

Background: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. Patients and methods: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. Results: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. Conclusion: With ∼5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-re

Published
2023

5. IL-8 secretion in primary cultures of prostate cells is associated with prostate cancer aggressiveness

Author

Neveu B, Moreel X, Deschênes-Rompré M-P, Bergeron A, LaRue H, Ayari C, Fradet Y, and Fradet V

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Bertrand Neveu*, Xavier Moreel*, Marie-Pier Deschênes-Rompré, Alain Bergeron, Hélène LaRue, Cherifa Ayari, Yves Fradet, Vincent FradetDepartment of Surgery, Laval University Cancer Research Centre, CHU de Quebec Research Centre, Quebec, QC, Canada *These authors contributed equally to this workBackground: Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness.Materials and methods: Short-term primary cell cultures of normal epithelial prostate cells were derived from prostate biopsies from 25 men undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded viral RNA and a potent inducer of the inflammatory response. Secretion of interleukin (IL)-8 in the cell culture medium by untreated and treated cells was measured and we determined the association between IL-8 levels in these primary cell cultures and prostate cancer characteristics. The Fligner–Policello test was used to compare the groups.Results: Baseline and induced IL-8 secretion were highly variable between cultured cells from different patients. This variation was not related to drug use, past medical history, age, or preoperative prostate-specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal cultured epithelial cells was associated with prostate cancer aggressiveness (P=0.0005).Conclusion: The baseline secretion of IL-8 from normal prostate epithelial cells in culture is strongly correlated with cancer aggressiveness and may drive prostate cancer carcinogenesis. A better characterization of individual prostate microenvironment may provide a basis for personalized treatment and for monitoring the effects of strategies aimed at preventing aggressive prostate cancer.Keywords: cancer aggressiveness, inflammation, interleukin 8, primary cell culture

Published
2014

6. 1747P Impact of prior chemotherapy (Chemo) on pembrolizumab (Pembro) response in urothelial cancer (UC): Exploratory analysis of the phase III KEYNOTE-045 study

Author

De Wit, R., primary, Vaughn, D.J., additional, Fradet, Y., additional, Fong, L., additional, Vogelzang, N.J., additional, Climent Duran, M.A., additional, Necchi, A., additional, Petrylak, D.P., additional, Gerritsen, W.R., additional, Gurney, H.P., additional, Quinn, D.I., additional, Culine, S., additional, Sternberg, C.N., additional, Bajorin, D.F., additional, Choueiri, T.K., additional, Xu, J., additional, Imai, K., additional, Homet Moreno, B., additional, Bellmunt, J., additional, and Lee, J-L., additional

Published
2022
Full Text
View/download PDF

11. 744P Association between gene expression signatures (sigs) and pembrolizumab (pembro) efficacy in patients (pts) with advanced urothelial cancer (UC)

Author

Grivas, P., primary, Balar, A.V., additional, Vuky, J., additional, de Wit, R., additional, Vogelzang, N.J., additional, Choueiri, T.K., additional, Bajorin, D., additional, Castellano Gauna, D., additional, Gerritsen, W., additional, Gurney, H., additional, Quinn, D.I., additional, Culine, S., additional, Fradet, Y., additional, Saadatpour, A., additional, Loboda, A., additional, Ma, J., additional, Rajasagi, M., additional, Godwin, J.L., additional, Moreno, B.H., additional, and Bellmunt, J., additional

Published
2020
Full Text
View/download PDF

12. 747P Association of TMB with efficacy of pembrolizumab (pembro) in patients (pts) with advanced urothelial cancer (UC): Results from KEYNOTE-045 and KEYNOTE-052

Author

Bellmunt, J., primary, de Wit, R., additional, Fradet, Y., additional, Climent, M.A., additional, Petrylak, D.P., additional, Lee, J-L., additional, Fong, L., additional, Necchi, A., additional, Sternberg, C.N., additional, Grivas, P., additional, O’Donnell, P.H., additional, Powles, T., additional, Plimack, E.R., additional, Cristescu, R., additional, Lunceford, J., additional, Ma, J., additional, Rajasagi, M., additional, Godwin, J.L., additional, Moreno, B.H., additional, and Bajorin, D., additional

Published
2020
Full Text
View/download PDF

13. LBA23 Pembrolizumab (P) combined with chemotherapy (C) vs C alone as first-line (1L) therapy for advanced urothelial carcinoma (UC): KEYNOTE-361

Author

Alva, A., primary, Csőszi, T., additional, Ozguroglu, M., additional, Matsubara, N., additional, Geczi, L., additional, Cheng, S.Y-S., additional, Fradet, Y., additional, Oudard, S., additional, Vulsteke, C., additional, Morales Barrera, R., additional, Fléchon, A., additional, Gunduz, S., additional, Loriot, Y., additional, Rodriguez-Vida, A., additional, Mamtani, R., additional, Yu, E.Y., additional, Nam, K., additional, Imai, K., additional, Moreno, B.H., additional, and Powles, T.B., additional

Published
2020
Full Text
View/download PDF

14. The prevalence of cardiovascular disease and its risk factors among prostate cancer patients treated with and without androgen deprivation

Author

Pinthus, J., primary, Shayegan, B., additional, Klotz, L., additional, Siemens, R., additional, Luke, P., additional, Niazi, T., additional, Fradet, V., additional, Fradet, Y., additional, Duceppe, E., additional, Lavallee, L., additional, Mousavi, N., additional, Hamilton, R., additional, Brown, I., additional, Gopaul, D., additional, Violette, P., additional, Davis, M., additional, Mian, R., additional, Karampatos, S., additional, and Darryl, L., additional

Published
2020
Full Text
View/download PDF

16. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer

Author

Fizazi, Karim, Tran, Namphuong, Fein, Luis, Matsubara, Nobuaki, Rodriguez Antolin, Alfredo, Alekseev, Boris Y., Özgã¼roglu, Mustafa, Dingwei, Ye, Feyerabend, Susan, Protheroe, Andrew, De Porre, Peter, Kheoh, Thian, Park, Youn C., Todd, Mary B., Chi, Korbenfeld E, Kim N., Metrebian, S, Kaen, L, Staneloni, E, Batagelj, E, Tan, H, Hovey, E, Woo, H, Frydenberg, M, Chua, W, D’Hondt, L, Evaraert, E, Verschaeve, V, Wynendaele, W, Schrijvers, D, Waltregny, D, Whenham, N, Demey, W, Franke, F, Panhoca, R, Damião, R, Zucca, L, Da Rosa, V, Reis, R, Scalabrini, A, Nahas, W, Girotto, G, Nogueira, A, Gomes, A, Coradazzi, A, Kurteva, G, Siemens, R, Gingerich, J, Fleshner, N, Fradet, Y, Morgan, S, North, S, Saad, F, Shayegan, B, Zalewski, P, Pinochet, R, Orellana, N, Ding, Q, Ye, Z, Xie, L, Du, C, Chen, Z, Huang, Y, Sun, Z, Li, H, Jin, J, Li, C, Wan, B, Tian, Y, Zhou, F, Xie, K, Yao, X, Qiu, M, Zou, Q, Na, Y, Sun, Y, Xue, B, Ma, L, Martinez, C, Salazar, M, Larios, C, Solano, S, Pavlik, I, Brodak, M, Hora, M, Büchler, T, Borre, M, Johansen, J, Mejlholm, I, Poulsen, M, Wittendorf, He, Tammela, T, Vaarala, M, Theodore, C, Staudacher, L, Villers, A, Laplaige, P, Suttman, H, Steuber, T, Natale, S, Jones, R, Tran, A, Mazhar, D, Mills, J, Nyirady, P, Salamon, C, Torzsok, F, Feher, J, Géczi, L, Lakatos, A, Keizman, D, Sella, A, Frank, S, Peer, A, Rosenbaum, E, Berger, R, Mermershtain, W, Carteni, G, Tonini, G, De Giorgi, U, Facchini, G, Berruti, Alfredo, Bracarda, S, Basso, U, Galli, L, Tortora, G, Alietta, M, Fukasawa, S, Suzuki, H, Hasumi, H, Tsuchiya, T, Uemura, H, Kanayama, H, Hashine, K, Sato, F, Matsumoto, H, Oya, M, Lee, Jl, Park, S, Keam, B, Yun, H, Kim, Y, Kang, B, Lee, K, Kim, C, Saad, M, Sundram, M, Calvo, D, Moreno, R, Rodriquez, J, Hernandez, C, van den Berg, H, De La Rosett, J, Van Moorse, R, Hunting, J, Hendriks, M, Kueppers, F, Gilling, P, Beaven, A, Holmes, M, Jassem, J, Oszukowska, E, Niezabitowski, J, Jaxa Larecka, D, Chwalinski, M, Swiniarski, P, Silva, C, Conceicãoa, P, Fraga, A, Mauricio, J, Rodrigues, T, Pinheiro, L, Lima, E, Palma Dos Reis, J, Volovat, C, Jinga, V, Harza, M, Alyasova, A, Budnik, N, Bychkov, Y, Izmaylov, A, Khvorosten, D, Matveev, V, Novsov, A, Vladimirov, V, Tevs, D, Sheveleva, L, Bulanov, A, Semenov, A, Fadeeva, N, Kulikov, E, Emelyanov, S, Karyakin, O, Shirinkin, V, Shkolnik, M, Lykov, A, Skopin, P, Kopyltsov, E, Mincik, I, Mir, O, Kliment, J, Mikurcik, E, Gajdos, M, Milichovsky, I, Malan, J, Bahlmann, J, Moshokoa, E, Madlala, T, Coetzee, L, Ribal, M, Miñana, B, Martinez Breijo, S, Carballido, J, Olmos, D, Requena, M, Morote, J, Damber, Je, Haggman, M, Nyman, C, Ljungberg, B, Bjartell, A, Ozen, H, Beduk, Y, Sozen, S, Cetinkaya, M, Ozyurt, M, Tansug, Z, Mungan, A, Tanidir, Y, Toktas, M, Hotko, E, Stus, V, Lyulko, O, Vinnyk, Y, Shparyk, Y, Sakalo, V, Bondarenko, I, Paramonov, V, Khareba, G, Hodos, V., Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, Tampere University, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'oncologie médicale

Subjects
Adult, Male, medicine.medical_specialty, Prednisolone, Kirurgia, anestesiologia, tehohoito, radiologia - Surgery, anesthesiology, intensive care, radiology, Abiraterone Acetate, 030232 urology & nephrology, Urology, 03 medical and health sciences, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, Prednisone, Antineoplastic Combined Chemotherapy Protocols, 80 and over, medicine, Humans, Aged, Aged, 80 and over, Androgen Antagonists, Middle Aged, Neoplasm Metastasis, Prostatic Neoplasms, Steroid 17-alpha-Hydroxylase, Survival Analysis, Medicine (all), Gynecology, business.industry, Apalutamide, Abiraterone acetate, General Medicine, medicine.disease, Interim analysis, Clinical trial, Darolutamide, chemistry, 030220 oncology & carcinogenesis, business, medicine.drug
Abstract

Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P

Published
2017
Full Text
View/download PDF

17. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Author

Powles, T. van der Heijden, M.S. Castellano, D. Galsky, M.D. Loriot, Y. Petrylak, D.P. Ogawa, O. Park, S.H. Lee, J.-L. De Giorgi, U. Bögemann, M. Bamias, A. Eigl, B.J. Gurney, H. Mukherjee, S.D. Fradet, Y. Skoneczna, I. Tsiatas, M. Novikov, A. Suárez, C. Fay, A.P. Duran, I. Necchi, A. Wildsmith, S. He, P. Angra, N. Gupta, A.K. Levin, W. Bellmunt, J. van der Heijden, M.S. Lee, J.L. Eigl, B.J. Mukherjee, S.D. Suarez, C. Westgeest, H. Flechon, A. Ou, Y.-C. Park, I. Matveev, V. Pérez-Valderrama, B. Cheng, S. Frank, S. Anido, U. Hamzaj, A. Retz, M. Sridhar, S. Scagliotti, G.V. Voortman, J. Alekseev, B. Alyasova, A. Komyakov, B. Dumez, H. Pavic, M. Kimura, G. Mizokami, A. Osanto, S. Arranz, J.A. Piersma, D. Shin, S.J. Karyakin, O. Delgado, I. Gonzalez, J.L. Pang, S.-T. Tran, A. Lipatov, O. Su, W.-P. Flaig, T. Alva, A. Park Kyong, H. Kopyltsov, E. Almagro, E. Domenech, M. Chang, Y.-H. Sautois, B. Ravaux, A. Aravantinos, G. Georgoulias, V. Mulder, S. Kim, Y.J. Kater, F. Chevreau, C. Tagawa, S. Zalewski, P. Joly, F. Hatiboglu, G. Gianni, L. Morelli, F. Tambaro, R. Hashimoto, Y. Nosov, A. Font, A. Rodriguez-Vida, A.M. Jones, R. Vasudev, N. Srinivas, S. Zhang, J. Gil, T. Finch, D. Grimm, M.-O. Su, Y.-L. Chowdhury, S. Hocking, C. Plas, E. North, S. Jensen, N.V. Theodore, C. Imkamp, F. Peer, A. Kobayashi, T. Sakai, H. Sassa, N. Yoshimura, K. Aarts, M. Ferreira Castro, A. Topuzov, M. Rodriguez, J.F. Vazquez, F.J. Tsai, Y.-C. Crabb, S. Hussain, S. Bendell, J. Gross-Goupil, M. Gwenaelle, G. Berger, R. Statsenko, G. Evans, L. Drakaki, A. Somer, B. Davis, I. Lynam, J. Borges, G. Dettino, A. Fay, A.P. Martins, G. Zucca, L.E. Agerbaek, M. Kalofonos, H. Rosenbaum, E. Enokida, H. Kikukawa, H. Nishimura, K. Tamada, S. Uemura, M. Lopez, Y. Gietema, J. Slojewski, M. Fernandes, I. Smolin, A. Mazhar, D. Kalebasty, A.R. Carthon, B. Loidl, W. Franke, F. Girotto, G. Alimohamed, N. Macfarlane, R. Pappot, H. Niegisch, G. Mavroudis, D. Sella, A. Porta, C. Ebara, S. Nakamura, M. Obara, W. Okuno, N. Shinohara, N. Sugimoto, M. Suzuki, A. Tokuda, N. Uemura, H. Yamaguchi, A. Ramirez, F. Rozanowski, P. Wiechno, P. Keam, B. Kislov, N. Plaksin, D. Cicin, I. Kumar, S. Galsky, M.D. Petrylak, D.P. Rosales, J. Vaishampayan, U. Culine, S. Papandreou, C. Nara, T. Erman, M. Kreiger, L. Janoski, J. Rosa, D. Siqueira, M. Canil, C. Sengelov, L. Tourani, J.-M. Arai, G. Hashine, K. Kawakita, M. Nakaigawa, N. Nomi, H. Shiina, H. Suzuki, H. Yonese, J. Kuri, R. Macedo, E. Rivera, S. Villalobos Prieto, A. Polakiewicz-Gilowska, A. Zaucha, R. Lopes, F. Ponomarev, R. Pomerantz, M. Shariat, S. Luk, C. Lesniewski-Kmak, K.

Abstract

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (

Published
2020

18. Abstracts

Author

Kavanagh, Brian P., Ngo, Cuong, Raymer, Karen, Yang, Homer, Alhashemi, Jamal A., Lui, Anne C. P., Reid, Dennis, Cicutti, Nicholas, Krepski, Barbra, Wood, Gordon, Heyland, Daren K., Badner, Neal H., Murkin, John M., Mohr, Jim, McKenzie, F. Neil, van der Starre, Peter J. A., van Rooyen-Butijn, W. T., Wilson-Yang, Kristine, Teoh, Kevin, Lee, R. M. K. W., Hossain, Imtiaz, Cheng, Davy, Karski, Jacek, Asokumar, Buvanendran, Sandier, Alan, St-Amand, Marc A., Murkin, John M., Menkis, Alan H., Downey, Donal B., Nantau, William, Adams, Sandy, Dowd, Noreen, Cheng, Davy, Wong, David, Carroll-Munro, Jo, Trachuk, Clare, Cregg, N., Cheng, D. C. H., Williams, W. G., Karski, J. M., Siu, S., Webb, G., Cheng, Davy C. H., Wong, David T., Kustra, Rafal, Karski, Jacek, Tibshirani, Robert J., Côté, Dany L., Lacey, David E., LeDez, Kenneth M., Smith, Julia A., Crosby, Edward T., Orkin, Fredrick K., Fisher, A., Volgyesi, G., Silverman, J., Edelstein, S., Rucker, J., Sommer, L., Dunington, S., Roy, L., Crochetière, C., Arsenault, M. -Y., Villeneuve, E., Lortie, L., Grange, Caroline S., Douglas, M. Joanne, Adams, Timothy J., Merrick, Pamela M., Lucas, S. Brian, Morgan, Pamela J., Halpern, Stephen, Lo, Jason, Giesinger, Carolyn L., Halpern, Stephen H., Breen, Terrance W., Vishnubala, Srigowri, Shetty, Geeta R., De Kock, M., Lagmiche, A., Scholtes, J. L., Grodecki, Wlodzimierz, Duffy, Peter J., Hull, Kathryn A., Hawboldt, Geoffrey S., Clark, Alexander J., Smith, J. Bruce, Norman, Richard W., Beattie, W. Scott, Sandier, A., Jewett, M., Valiquette, L., Katz, J., Fradet, Y., Redelmeier, D., Sampson, H., Cole, Jeff, Chedore, Todd, Snedden, Walter, Green, Robert G., Sosis, Mitchel B., Robles, Philip I., Lazar, Edward R., Jolly, Donald T., Tarn, Yun K., Tawfik, Soheir R., Clanachan, Alexander S., Milne, Avaleigh, Beamish, Travis, Cuillerier, D. J., Sharpe, M. D., Lee, J. K., Basta, M., Krahn, A. D., Klein, G. J., Yee, R., Vakharia, Narendra, Francis, Heather, Scheepers, Louis, Vaghadia, Himat, Carrier, Joanne, Martin, René, Pirlet, Marline, Claprood, Yves, Tétrault, Jean-Pierre, Wong, T. D., Ryner, L., Kozlowski, P., Scarth, G., Warrian, R. K., Lefevre, G., Thiessen, D., Girling, L., Doiron, L., McCudden, C., Saunders, J., Mutch, W. A. C., Duffy, Peter J., Langevin, Stéphan, Lessard, Martin R., Trépanier, Claude A., Hare, Gregory M. T., Ngan, Johnson C. S., Viskari, Dan, Berrill, A., Jodoin, Christian, Couture, Jacques, Bellemare, François, Farmer, Stephen, Muir, Holly, Money, Phyllis, Milne, Brian, Parlow, Joel, Raymond, Jennifer, Williams, Julie M., Craen, Rosemary A., Novick, Teresa, Komar, Wendy, Frenette, Luc, Cox, Jerry, Lockhart, B., McArdle, P., Eckhoff, D., Bynon, S., Dobkowski, Wojciech B., Grant, David R., Wall, William J., Chedrawy, Edgar G., Hall, Richard I., Nedelcu, Vivian, Parlow, Joel, Viale, Jean-Paul, Bégou, Gérard, Sagnard, Pierre, Hughson, Richard, Quintin, Luc, Troncy, Éric, Collet, Jean-Paul, Shapiro, Stan, Guimond, Jean-Gilles, Blair, Louis, Ducruet, Thiérry, Francœur, Martin, Charbonneau, Marc, Blaise, Gilbert, Snedden, W., Bernadska, E., Manson, H. I., Kutt, Juditli L., Mezon, Beruie Y., Nishida, Osamu, Arellano, Ramiro, Boylen, Patty, DeMajo, Wilfred, Archer, David P., Roth, Sheldon H., Raman, Sitaram, Manninen, Pirjo, Boyle, Kevin, Cenic, Aleksa, Lee, Ting-Yim, Gelb, Adrian W., Reinders, F. X., Brown, J. I. M., Baker, A. J., Moulton, R. J., Schlichtert, L., Schwarz, Stephan K. W., Puil, Ernest, Finegan, Barry A., Finucane, Brendan T., Kurrek, Matt M., Devitt, J. Hugh, Morgan, Pamela J., Cleave-Hogg, Doreen, Bradley, John, Byrick, Robert, Spadafora, Salvatore M., Fuller, John G., Gelula, Mark H., Mayson, Kelly, Forster, Bruce, Byrick, R. J., McKnight, D. J., Kurrek, M., Kolton, M., Cleave-Hogg, D., Haughton, J., Halpern, S., Kronberg, J., Shysh, Sandy, Eagle, Chris, Dagnone, A. Joel, Parlow, Joel L., Blaise, G., Yang, F., Nguyen, H., Troncy, E., Czaika, G., Wachowski, Ireneusz, Basta, M., Krahn, A. D., Yee, R., Deladrière, Hervé, Cambier, Chantal, Pendeville, Philippe, Hung, O. R., Coonan, E., Whynot, S. C., Mezei, M., Coonan, E., Whynot, S. C., Ho, Anthony M. -H., Luchsinger, Ingrid S., Ling, Elizabeth, Mashava, Doreen, Chinyanga, Herbert M., Cohen, Marsha M., Shaw, Melissa, Robblee J. A., Labow R. S., Rubens F. D., Diemunsch, A. M., Gervais, R., Rose, D. K., Cohen, M. M., O’Brien-Pallas, L., Copplestone, C., Rose, D. K., Karkouti, K., Sykora, K., Cheung, Shirley L. W., Booker, Peter D., Franks, Roger, Pozzi, Marco, Guard, Beverley, Sikich, Nancy, Lerman, Jerrold, Levine, Mark, Swan, Hilton, Cox, Peter, Montgomery, Carolyne, Dunn, Gillian, Bourne, Russell, Kinahan, Anna, McCormack, James, Dunn, Gillian S., Reimer, Eleanor J., Sanderson, Peter, Sanderson, Peter M., Montgomery, Carolyne J., Betts, Terri A., Orlay, Guy R., Wong, David H., Cohen, Marsha, Al-Kaisy, A. A., Chan, V., Peng, P., Perlas, A., Miniad, A., Cushing, Edward V., Mills, Keith R., El-Beheiry, Hossam, Jahromi, Shokrollah S., Weaver, John, Morris, Mary, Carien, Peter L., Cowan, Robert McTaggart, Manninen, Pirjo, Richards, Jonathan, Robblee, J. A., Labow, R. S., Rubens, F. D., Menkis, Alan H., Adams, Sandy, Henderson, Blair T., Hudson, Robert J., Thomson, Ian R., Moon, Michael, Peterson, Mark D., Rosenbloom, Morley, Davison, Patrick J., Ali, Mohamed, Ali, Naheed S., Searle, Norman R., Thomson, Ian, Roy, Micheline, Gagnon, Line, Lye, A., Walsh, F., Middleton, W., Wong, D., Langer, A., Errett, L., Mazer, C. D., Karski, Jacek, Tibshirani, Robert J., Williamson, Karin M., Smith, Graham, Gnanendran, Kandiah P., Bignell, S. J., Jones, S., Sleigh, J., Arnell, M., Schultz, Jan-Ake I., Fear, David W., Ganapathy, S., Moote, C., Wassermann, R., Watson, J., Armstrong, K., Calikyan, Aznif Ozsolak, Yilmaz, Oya, Kose, Yildiz, Peng, Philip, Chan, Vincent, Chung, Frances, Claxton, Andrew R., Krishnathas, Ananthan, Mezei, Gabor, Badner, Neal H., Paul, Terri L., Doyle, Jacqueline A., Mehta, Mahesh, DeLima, Luiz G. R., Silva, Lucia E. O., May, Warren L., Maliakkal, Roy J., Mehta, Mahesh, Kolesar, Richard, Arellano, Ramiro, Rafuse, Sara, Fletcher, Mary, Dunn, Geoffrey, Curran, Michael, Bragg, Paul, Chamberlain, Wayne, Crossan, MaryLou, Ganapathy, S., Sandhu, H., Spadafora, S., Mian, R., Evans, B., Hurst, L., and Katsiris, S.

Published
1997
Full Text
View/download PDF

19. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Author

Powles, T. van der Heijden, M.S. Castellano, D. Galsky, M.D. Loriot, Y. Petrylak, D.P. Ogawa, O. Park, S.H. Lee, J.-L. De Giorgi, U. Bögemann, M. Bamias, A. Eigl, B.J. Gurney, H. Mukherjee, S.D. Fradet, Y. Skoneczna, I. Tsiatas, M. Novikov, A. Suárez, C. Fay, A.P. Duran, I. Necchi, A. Wildsmith, S. He, P. Angra, N. Gupta, A.K. Levin, W. Bellmunt, J. van der Heijden, M.S. Lee, J.L. Eigl, B.J. Mukherjee, S.D. Suarez, C. Westgeest, H. Flechon, A. Ou, Y.-C. Park, I. Matveev, V. Pérez-Valderrama, B. Cheng, S. Frank, S. Anido, U. Hamzaj, A. Retz, M. Sridhar, S. Scagliotti, G.V. Voortman, J. Alekseev, B. Alyasova, A. Komyakov, B. Dumez, H. Pavic, M. Kimura, G. Mizokami, A. Osanto, S. Arranz, J.A. Piersma, D. Shin, S.J. Karyakin, O. Delgado, I. Gonzalez, J.L. Pang, S.-T. Tran, A. Lipatov, O. Su, W.-P. Flaig, T. Alva, A. Park Kyong, H. Kopyltsov, E. Almagro, E. Domenech, M. Chang, Y.-H. Sautois, B. Ravaux, A. Aravantinos, G. Georgoulias, V. Mulder, S. Kim, Y.J. Kater, F. Chevreau, C. Tagawa, S. Zalewski, P. Joly, F. Hatiboglu, G. Gianni, L. Morelli, F. Tambaro, R. Hashimoto, Y. Nosov, A. Font, A. Rodriguez-Vida, A.M. Jones, R. Vasudev, N. Srinivas, S. Zhang, J. Gil, T. Finch, D. Grimm, M.-O. Su, Y.-L. Chowdhury, S. Hocking, C. Plas, E. North, S. Jensen, N.V. Theodore, C. Imkamp, F. Peer, A. Kobayashi, T. Sakai, H. Sassa, N. Yoshimura, K. Aarts, M. Ferreira Castro, A. Topuzov, M. Rodriguez, J.F. Vazquez, F.J. Tsai, Y.-C. Crabb, S. Hussain, S. Bendell, J. Gross-Goupil, M. Gwenaelle, G. Berger, R. Statsenko, G. Evans, L. Drakaki, A. Somer, B. Davis, I. Lynam, J. Borges, G. Dettino, A. Fay, A.P. Martins, G. Zucca, L.E. Agerbaek, M. Kalofonos, H. Rosenbaum, E. Enokida, H. Kikukawa, H. Nishimura, K. Tamada, S. Uemura, M. Lopez, Y. Gietema, J. Slojewski, M. Fernandes, I. Smolin, A. Mazhar, D. Kalebasty, A.R. Carthon, B. Loidl, W. Franke, F. Girotto, G. Alimohamed, N. Macfarlane, R. Pappot, H. Niegisch, G. Mavroudis, D. Sella, A. Porta, C. Ebara, S. Nakamura, M. Obara, W. Okuno, N. and Powles, T. van der Heijden, M.S. Castellano, D. Galsky, M.D. Loriot, Y. Petrylak, D.P. Ogawa, O. Park, S.H. Lee, J.-L. De Giorgi, U. Bögemann, M. Bamias, A. Eigl, B.J. Gurney, H. Mukherjee, S.D. Fradet, Y. Skoneczna, I. Tsiatas, M. Novikov, A. Suárez, C. Fay, A.P. Duran, I. Necchi, A. Wildsmith, S. He, P. Angra, N. Gupta, A.K. Levin, W. Bellmunt, J. van der Heijden, M.S. Lee, J.L. Eigl, B.J. Mukherjee, S.D. Suarez, C. Westgeest, H. Flechon, A. Ou, Y.-C. Park, I. Matveev, V. Pérez-Valderrama, B. Cheng, S. Frank, S. Anido, U. Hamzaj, A. Retz, M. Sridhar, S. Scagliotti, G.V. Voortman, J. Alekseev, B. Alyasova, A. Komyakov, B. Dumez, H. Pavic, M. Kimura, G. Mizokami, A. Osanto, S. Arranz, J.A. Piersma, D. Shin, S.J. Karyakin, O. Delgado, I. Gonzalez, J.L. Pang, S.-T. Tran, A. Lipatov, O. Su, W.-P. Flaig, T. Alva, A. Park Kyong, H. Kopyltsov, E. Almagro, E. Domenech, M. Chang, Y.-H. Sautois, B. Ravaux, A. Aravantinos, G. Georgoulias, V. Mulder, S. Kim, Y.J. Kater, F. Chevreau, C. Tagawa, S. Zalewski, P. Joly, F. Hatiboglu, G. Gianni, L. Morelli, F. Tambaro, R. Hashimoto, Y. Nosov, A. Font, A. Rodriguez-Vida, A.M. Jones, R. Vasudev, N. Srinivas, S. Zhang, J. Gil, T. Finch, D. Grimm, M.-O. Su, Y.-L. Chowdhury, S. Hocking, C. Plas, E. North, S. Jensen, N.V. Theodore, C. Imkamp, F. Peer, A. Kobayashi, T. Sakai, H. Sassa, N. Yoshimura, K. Aarts, M. Ferreira Castro, A. Topuzov, M. Rodriguez, J.F. Vazquez, F.J. Tsai, Y.-C. Crabb, S. Hussain, S. Bendell, J. Gross-Goupil, M. Gwenaelle, G. Berger, R. Statsenko, G. Evans, L. Drakaki, A. Somer, B. Davis, I. Lynam, J. Borges, G. Dettino, A. Fay, A.P. Martins, G. Zucca, L.E. Agerbaek, M. Kalofonos, H. Rosenbaum, E. Enokida, H. Kikukawa, H. Nishimura, K. Tamada, S. Uemura, M. Lopez, Y. Gietema, J. Slojewski, M. Fernandes, I. Smolin, A. Mazhar, D. Kalebasty, A.R. Carthon, B. Loidl, W. Franke, F. Girotto, G. Alimohamed, N. Macfarlane, R. Pappot, H. Niegisch, G. Mavroudis, D. Sella, A. Porta, C. Ebara, S. Nakamura, M. Obara, W. Okuno, N.

Abstract

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 2

Published
2020

29. Three-year follow-up from the phase III KEYNOTE-045 trial: Pembrolizumab (Pembro) versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC)

Author

Necchi, A., primary, Fradet, Y., additional, Bellmunt, J., additional, de Wit, R., additional, Lee, J.-L., additional, Fong, L., additional, Vozelgang, N.J., additional, Climent, M.A., additional, Petrylak, D.P., additional, Choueiri, T.K., additional, Gerritsen, W.R., additional, Gurney, H., additional, Quinn, D.I., additional, Culine, S., additional, Sternberg, C.N., additional, Nam, K., additional, Frenkl, T.L., additional, Godwin, J.L., additional, Bajorin, D.F., additional, and Vaughn, D.J., additional

Published
2019
Full Text
View/download PDF

30. Raman microscopy for the identification of an aggressive variant of prostate cancer, intraductal carcinoma of the prostate

Author

Trudel, D., primary, Grosset, A.-A., additional, Dallaire, F., additional, Nguyen, T., additional, Kougioumoutzakis, A., additional, Azzi, F., additional, Aubertin, K., additional, Saad, F., additional, Latour, M., additional, Albadine, R., additional, Boutros, P., additional, Fraser, M., additional, Bristow, R., additional, Van der Kwast, T., additional, Benzerdjeb, N., additional, Hovington, H., additional, Bergeron, A., additional, Fradet, Y., additional, Brisson, H., additional, and Leblond, F., additional

Published
2019
Full Text
View/download PDF

33. 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

Author

Fradet, Y., Bellmunt, J., Vaughn, D.J., Lee, J.L., Fong, L., Vogelzang, N.J., Gerritsen, W.R., Wit, R. de, Bajorin, D.F., Fradet, Y., Bellmunt, J., Vaughn, D.J., Lee, J.L., Fong, L., Vogelzang, N.J., Gerritsen, W.R., Wit, R. de, and Bajorin, D.F.

Abstract

Contains fulltext : 207335.pdf (publisher's version ) (Open Access)

Published
2019

34. Impact of prognostic factors and risk groups on overall survival (OS) in patients treated with pembrolizumab vs investigator’s choice chemotherapy for advanced urothelial cancer (UC): Post hoc analysis of KEYNOTE-045

Author

Bellmunt, J., primary, de Wit, R., additional, Vaughn, D.J., additional, Fradet, Y., additional, Lee, J.L., additional, Fong, L., additional, Vogelzang, N.J., additional, Climent, M.A., additional, Petrylak, D., additional, Choueiri, T.K., additional, Necchi, A., additional, Gerritsen, W.R., additional, Gurney, H., additional, Quinn, D.I., additional, Culine, S., additional, Sternberg, C.N., additional, Jensen, E., additional, Frenkl, T., additional, Perini, R.F., additional, and Bajorin, D., additional

Published
2018
Full Text
View/download PDF

36. Increased prostate cancer glucose metabolism detected by FDG-PET/CT in localised Gleason 8-10 prostate cancers identifies very high-risk patients for early recurrence and resistance to castration

Author

Lavallee, E., primary, Bergeron, M., additional, Buteau, F.-A., additional, Duchesnay, N., additional, Blouin, A.-C., additional, Fradet, Y., additional, Dujardin, T., additional, Tiguert, R., additional, Lacombe, L., additional, Fradet, V., additional, Makao-Nguile, M., additional, Beauregard, J.-M., additional, and Pouliot, F., additional

Published
2018
Full Text
View/download PDF

37. Subgroup analyses from KEYNOTE-045: Pembrolizumab (pembro) versus individual investigator’s choice of chemotherapy (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (uc)

Author

Petrylak, D., primary, Vogelzang, N.J., additional, Fradet, Y., additional, Bajorin, D., additional, de Wit, R., additional, Vaughn, D.J., additional, Lee, J-L., additional, Fong, L., additional, Climent, M.A., additional, Necchi, A., additional, Gerritsen, W.R., additional, Gurney, H., additional, Quinn, D.I., additional, Culine, S., additional, Sternberg, C.N., additional, Jensen, E., additional, Puhlmann, M., additional, Perini, R., additional, Bellmunt, J., additional, and Choueiri, T.K., additional

Published
2017
Full Text
View/download PDF

38. Pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer (UC): Mature results from the phase 3 KEYNOTE-045 trial

Author

de Wit, R., primary, Vaughn, D.J., additional, Fradet, Y., additional, Lee, J-L., additional, Fong, L., additional, Vogelzang, N.J., additional, Climent, M.A., additional, Petrylak, D.P., additional, Choueiri, T.K., additional, Necchi, A., additional, Gerritsen, W.R., additional, Gurney, H., additional, Quinn, D.I., additional, Culine, S., additional, Sternberg, C.N., additional, Mai, Y., additional, Puhlmann, M., additional, Perini, R.F., additional, Bellmunt, J., additional, and Bajorin, D.F., additional

Published
2017
Full Text
View/download PDF

39. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

Author

Bellmunt, J., Wit, R. de, Vaughn, D.J., Fradet, Y., Lee, J.L., Fong, L., Vogelzang, N.J., Climent, M.A., Petrylak, D.P., Choueiri, T.K., Necchi, A., Gerritsen, W.R., Gurney, H., Quinn, D.I., Culine, S., Sternberg, C.N., Mai, Y., Poehlein, C.H., Perini, R.F., Bajorin, D.F., Bellmunt, J., Wit, R. de, Vaughn, D.J., Fradet, Y., Lee, J.L., Fong, L., Vogelzang, N.J., Climent, M.A., Petrylak, D.P., Choueiri, T.K., Necchi, A., Gerritsen, W.R., Gurney, H., Quinn, D.I., Culine, S., Sternberg, C.N., Mai, Y., Poehlein, C.H., Perini, R.F., and Bajorin, D.F.

Abstract

Contains fulltext : 170338.pdf (publisher's version ) (Open Access), Background Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options. Methods In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4kappa isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more. Results The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also

Published
2017

40. 919P - Three-year follow-up from the phase III KEYNOTE-045 trial: Pembrolizumab (Pembro) versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer (UC)

Author

Necchi, A., Fradet, Y., Bellmunt, J., de Wit, R., Lee, J.-L., Fong, L., Vozelgang, N.J., Climent, M.A., Petrylak, D.P., Choueiri, T.K., Gerritsen, W.R., Gurney, H., Quinn, D.I., Culine, S., Sternberg, C.N., Nam, K., Frenkl, T.L., Godwin, J.L., Bajorin, D.F., and Vaughn, D.J.

Published
2019
Full Text
View/download PDF

43. p53 Predictive Value for pT1-2 N0 Disease at Radical Cystectomy

Author

Shariat, S. F., Lotan, Y., Karakiewicz, P. I., Ashfaq, R., Isbarn, H., Fradet, Y., Bastian, P. J., Nielsen, M. E., Capitanio, U., Jeldres, C., Müller, S. C., Karam, J. A., Heukamp, L. C., Netto, G., Lerner, S. P., Sagalowsky, A. I., Cote, R. J., MONTORSI , FRANCESCO, Shariat, S. F., Lotan, Y., Karakiewicz, P. I., Ashfaq, R., Isbarn, H., Fradet, Y., Bastian, P. J., Nielsen, M. E., Capitanio, U., Jeldres, C., Montorsi, Francesco, Müller, S. C., Karam, J. A., Heukamp, L. C., Netto, G., Lerner, S. P., Sagalowsky, A. I., and Cote, R. J.

Published
2009

44. Use of Markers in Defining Urothelial Premalignant and Malignant Conditions

Author

Tribukait B, Fradet Y, H. B. Grossman, and Schmitz-Dräger B

Subjects
Oncology, medicine.medical_specialty, Urology, Urinary Bladder, Population, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, medicine, Humans, education, Carcinoma, Transitional Cell, Clinical Trials as Topic, education.field_of_study, Urinary bladder, Bladder cancer, business.industry, Carcinoma in situ, Cancer, medicine.disease, Cell Transformation, Neoplastic, medicine.anatomical_structure, Urinary Bladder Neoplasms, Nephrology, Tumor progression, Dysplasia, Predictive value of tests, Disease Progression, business, Carcinoma in Situ
Abstract

Markers have revealed the presence of phenotypically abnormal areas in histologically benign urothelium in bladders containing transitional cell carcinomas. This finding strongly suggests that at least some bladder cancers are associated with changes in the field and that markers can detect these lesions before they reach a grossly malignant stage. Markers have been used clinically for the detection of cancer in patients who are under regular surveillance for recurrence of bladder cancer. Much less information is available regarding the use of markers to detect bladder cancer without a prior history of the disease and for the prediction of which tumors are biologically more aggressive. However, ongoing clinical trials are addressing the latter issue. The type of specimen and its preparation will determine what type of markers can be analyzed. Although marker performance is based upon sensitivity and specificity, the prevalence of bladder cancer in the population being tested will dramatically affect the positive predictive value of an assay. Markers with high positive predictive value are indicators for interventions, such as biopsy, while markers with high negative specific values are useful for avoiding interventions. Cytology is used to detect occult high-grade neoplasms such as carcinoma in situ. While not yet clinically validated, tests with high negative predictive value could be used to decrease the frequency of cystoscopic evaluation. Markers must be validated by testing them prospectively using previously defined cut-off values. Furthermore, markers that will be used to alter treatment should be tested prospectively to determine the safety and cost-effectiveness of this strategy. Recommendations for future work include: (1) evaluation of markers in patients with dysplasia defined by the current pathologic classification; (2) evaluation of markers as indicators of tumor recurrence; (3) evaluation of markers as indicators of tumor progression; and (4) evaluation of markers in chemoprevention studies.

Published
2000
Full Text
View/download PDF

46. Pembrolizumab vs investigator-choice chemotherapy for previously treated advanced urothelial cancer: Phase 3 KEYNOTE-045 study

Author

Necchi, A., primary, Bellmunt, J., additional, De Wit, R., additional, Vaughn, D., additional, Fradet, Y., additional, Lee, J.L., additional, Fong, L., additional, Vogelzang, N., additional, Climent, M., additional, Petrylak, D., additional, Choueiri, T., additional, Gerritsen, W., additional, Gurney, H., additional, Quinn, D., additional, Culine, S., additional, Sternberg, C., additional, Mai, Y., additional, Puhlmann, M., additional, Perini, R., additional, and Bajorin, D., additional

Published
2017
Full Text
View/download PDF

47. Prognostic Significance of Tonsil Expression and the Homologous Recombination Pathway in Intermediate-Risk Prostate Cancer Recurrence

Author

So, J., primary, Chua, M.L.K., additional, Lalonde, E., additional, Pra, A. Dal, additional, Berlin, A., additional, Orain, M., additional, Hovington, H., additional, Bergeron, A., additional, Fradet, Y., additional, Têtu, B., additional, Meng, A., additional, Zhang, J., additional, Zafarana, G., additional, Livingstone, J., additional, Pintilie, M., additional, van der Kwast, T., additional, Fraser, M., additional, Boutros, P.C., additional, and Bristow, R.G., additional

Published
2016
Full Text
View/download PDF

48. 901P - Impact of prognostic factors and risk groups on overall survival (OS) in patients treated with pembrolizumab vs investigator’s choice chemotherapy for advanced urothelial cancer (UC): Post hoc analysis of KEYNOTE-045

Author

Bellmunt, J., de Wit, R., Vaughn, D.J., Fradet, Y., Lee, J.L., Fong, L., Vogelzang, N.J., Climent, M.A., Petrylak, D., Choueiri, T.K., Necchi, A., Gerritsen, W.R., Gurney, H., Quinn, D.I., Culine, S., Sternberg, C.N., Jensen, E., Frenkl, T., Perini, R.F., and Bajorin, D.

Published
2018
Full Text
View/download PDF

49. CLINICAL NODAL STAGING SCORES FOR BLADDER CANCER: A PROPOSAL FOR PREOPERATIVE RISK-ASSESSMENT

Author

Rink, 1. 0. M., Ehdaie, B., Cha, E. K., Hansen, J., Svatek, R., Chromecki, T. F., Fajkovic, H., Novara, Giacomo, Daneshmand, S., Fradet, Y., Lotan, Y., Sagalowsky, A. I., Bastian, P. J., Kassouf, W., Fritsche, H. M., Burger, M., Izawa, J., Tilki, D., Abdollah, F., Chun, F. K., Sonpavde, G., Fisch, M., Scherr, D., Gonen, M., and Shariat, S. F.

Published
2012

50. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort

Author

Svatek, Rs, Shariat, Sf, Novara, Giacomo, Skinner, Ec, Fradet, Y, Bastian, Pj, Kamat, Am, Kassouf, W, Karakiewicz, Pi, Fritsche, Hm, Izawa, Ji, Tilki, D, Ficarra, Vincenzo, Volkmer, Bg, Isbarn, H, and Dinney, Cp

Subjects
Stage, medicine.medical_specialty, Survival, business.industry, Urology, medicine.medical_treatment, General surgery, MEDLINE, External validation, radical cystectomy, muscle invasive bladder cancer, Discrepancy, Migration, Surgery, Cystectomy, Cohort, medicine, Stage (cooking), business, Pathological
Published
2011

Catalog

Books, media, physical & digital resources
See catalog results