Perioperative pembrolizumab therapy in muscle-invasive bladder cancer: Phase III KEYNOTE-866 and KEYNOTE-905/EV-303.
Matthew D. Galsky,Christopher J. Hoimes,Andrea Necchi,Neal D. Shore,J. Alfred Witjes,Gary D. Steinberg,Jens Bedke,Hiroyuki Nishiyama,Xiao Fang,Ritesh S. Kataria,Eric Sbar,Xieyang Jia,Arlene O. Siefker-Radtke +12 more
Reads0
Chats0
TLDR
The randomized Phase III KEYNOTE-866 and KeyNOTE-905/EV-303 studies are being conducted to evaluate efficacy and safety of perioperative pembrolizumab or placebo with chemotherapy in cisplatin-ineligible patients with MIBC as discussed by the authors.Abstract:
Muscle-invasive bladder cancer (MIBC) is associated with high rates of recurrence and poor prognosis despite aggressive treatment. Neoadjuvant chemotherapy before radical cystectomy (RC) improves outcomes in cisplatin-eligible patients; however, the improvement in overall survival is modest. Standard of care for cisplatin-ineligible patients remains RC; more effective systemic therapies are needed. Recent Phase Ib/II studies suggest pembrolizumab monotherapy and combination therapy are effective neoadjuvant therapies for MIBC. The randomized Phase III KEYNOTE-866 and KEYNOTE-905/EV-303 studies are being conducted to evaluate efficacy and safety of perioperative pembrolizumab or placebo with chemotherapy in cisplatin-eligible patients with MIBC (KEYNOTE-866) and of pembrolizumab monotherapy versus pembrolizumab plus enfortumab vedotin versus RC plus pelvic lymph node dissection alone in cisplatin-ineligible patients with MIBC (KEYNOTE-905/EV-303). Clinical trial registration: NCT03924856 & NCT03924895 (ClinicalTrials.gov).read more
Citations
More filters
Journal ArticleDOI
Research Trends and Most Influential Clinical Studies on Anti-PD1/PDL1 Immunotherapy for Cancers: A Bibliometric Analysis
Yanhao Liu,Yan Xu,Xi Cheng,Yaru Lin,Shu Jiang,Haiming Yu,Zhen Zhang,Linlin Lu,Xiao-Tao Zhang +8 more
TL;DR: Non-small cell lung cancer and melanoma are the most well-studied cancers, while nivolumab and pembrolizumab are themost commonly investigated anti-PD1/PDL1 antibodies.
Journal ArticleDOI
Recent Advances in Medical Therapy for Urological Cancers
TL;DR: This review provides an overview of agents and regimens that have just launched or will be launched in the near future in Japan, based on the promising anti-tumor efficacy and manageable safety profiles being demonstrated in clinical trials, which are expected to be rapidly introduced in Japanese clinical practice.
Journal ArticleDOI
Immunotherapy for Bladder Cancer: Latest Advances and Ongoing Clinical Trials
TL;DR: The current state of the rapidly evolving field of immunotherapy in bladder cancer is summarized, highlighting novel approaches and ongoing trials in this exciting area of research.
Journal ArticleDOI
Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems
Yi Wei,Bastian Amend,Tilman Todenhöfer,Nizar Lipke,Wilhelm K. Aicher,Falko Fend,Arnulf Stenzl,Niklas Harland +7 more
TL;DR: It is concluded that organoids maintained inter-individual sensitivities towards venetoclax, S63845, and cisplatin, and it is also reported that two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses, and colorimetric assays yielded different IC50 toxicity levels when compared to chemiluminescence assays.
Journal ArticleDOI
Expressions of PD-L1 and Nectin-4 in urothelial cancer patients treated with pembrolizumab.
H. Ueki,Nobuyuki Hinata,Koichi Kitagawa,Takuto Hara,Tomoaki Terakawa,Junya Furukawa,Ken-ichi Harada,Y. Nakano,M. Komatsu,Masato Fujisawa,Toshiro Shirakawa +10 more
TL;DR: In this article, the association between immunohistochemical biomarkers and clinical outcomes in urothelial cancer patients treated with pembrolizumab was explored and the associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed.
References
More filters
Journal ArticleDOI
Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer
Jacqueline Vuky,Arjun Vasant Balar,Daniel Castellano,Peter H. O'Donnell,Petros Grivas,Joaquim Bellmunt,Thomas Powles,Dean F. Bajorin,Noah M. Hahn,Mary J. Savage,Xiao Fang,James Luke Godwin,Tara L. Frenkl,Blanca Homet Moreno,Ronald de Wit,Elizabeth R. Plimack +15 more
TL;DR: First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced UC and is associated with prolonged OS, particularly with PD-L1 CPS ≥ 10 and lymph node-only disease.
Journal ArticleDOI
EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma.
Jonathan E. Rosenberg,Srikala S. Sridhar,Jingsong Zhang,David Smith,D. Ruether,Thomas W. Flaig,Joaquina Baranda,Joshua M. Lang,Elizabeth R. Plimack,Randeep Sangha,Elisabeth I. Heath,J. Merchan,David I. Quinn,Sandy Srinivas,Matthew I. Milowsky,Chunzhang Wu,Elaina M. Gartner,Peiying Zuo,Amal Melhem-Bertrandt,Daniel P. Petrylak +19 more
TL;DR: Single-agent EV was generally well tolerated and provided clinically meaningful and durable responses in patients with mUC; survival data are encouraging and a pivotal phase II and a confirmatory phase III study are ongoing.
Journal ArticleDOI
Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses
Christian Pfister,Gwenaelle Gravis,Aude Fléchon,Michel Soulié,Laurent Guy,Brigitte Laguerre,Nicolas Mottet,Florence Joly,Yves Allory,V. Harter,Stéphane Culine,Vesper Trial Investigators +11 more
TL;DR: The toxicity of dd-MVAC was manageable with more severe asthenia and GI side effects than that of GC in perioperative chemotherapy; however, such data have to be confirmed on progression-free survival, with primary endpoint data expected in mid-2021.
Journal ArticleDOI
Epidemiology, aetiology and screening of bladder cancer
TL;DR: In conclusion, screening studies have suggested a survival benefit amongst screened non-symptomatic populations with known risk factors, but this has not become standard practice.
Journal ArticleDOI
Systemic, perioperative management of muscle-invasive bladder cancer and future horizons
TL;DR: Trial results have demonstrated the unprecedented ability of immune- checkpoint blockade to induce durable remissions in patients with metastatic disease that has progressed after chemotherapy; studies are now urgently needed to determine how best to incorporate this powerful therapeutic modality into the care of patients with MIBC.