For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
3
views
28
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      758
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      KEYNOTE-991: pembrolizumab plus enzalutamide and androgen deprivation for metastatic hormone-sensitive prostate cancer

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Current treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC) delays disease progression and improves survival, but resistance is inevitable. Additional therapies that prolong survival are needed. Androgen deprivation therapy (ADT) combined with next-generation hormonal agents, such as enzalutamide, is standard-of-care for men with mHSPC. Emerging evidence suggests potential synergism between enzalutamide and the PD-1 inhibitor pembrolizumab in prostate cancer. The phase III randomized, placebo-controlled, double-blind KEYNOTE-991 trial will investigate the efficacy and safety of pembrolizumab versus placebo in combination with enzalutamide when initiating ADT in participants with mHSPC naive to next-generation hormonal agents. Approximately 1232 patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks or placebo every 3 weeks, both with enzalutamide 160 mg once daily and ADT. Dual primary end points are overall survival and radiographic progression-free survival. Secondary end points include time to first subsequent therapy, time to symptomatic skeletal related event, objective response rate and safety and tolerability.

          Clinical Trial Registration: NCT04191096 ( ClinicalTrials.gov ).

          Abstract

          Tweetable abstract

          The randomized, double-blind, phase III KEYNOTE-991 study will investigate the efficacy and safety of pembrolizumab versus placebo in combination with enzalutamide when initiating androgen deprivation therapy in participants with metastatic hormone sensitive prostate cancer naive to next-generation hormonal agents.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
          Article 0 comments Cited 33374 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The blockade of immune checkpoints in cancer immunotherapy.

            Drew M Pardoll (2012)
            Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
            Article 0 comments Cited 5335 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

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

              Karim Fizazi, NamPhuong Tran, Luis Fein … (2017)
              Background 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. Methods 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. Results 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<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group. Conclusions The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).
              Article 0 comments Cited 470 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Christian Gratzke: (View ORCID Profile)
                Journal
                Title: Future Oncology
                Abbreviated Title: Future Oncology
                Publisher: Future Medicine Ltd
                ISSN (Print): 1479-6694
                ISSN (Electronic): 1744-8301
                Publication date Created: December 2022
                Publication date (Print): December 2022
                Volume: 18
                Issue: 37
                Pages: 4079-4087
                Affiliations
                [1 ]Department of Urology, University Hospital Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany
                [2 ]Szpital Wojewodzki im Mikolaja Kopernika, Chałubińskiego 7, Koszalin, 75-581, Poland
                [3 ]IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Via Piero Maroncelli, 40, Meldola, 47014, Italy
                [4 ]Oncocentro, Av. Pontes Vieira, 2551, Ceara, 60135-237, Brazil
                [5 ]Charite Universitaetsmedizin, Charitépl. 1, Berlin, 10117, Germany
                [6 ]Department of Urology, Medical University of Vienna, Spitalgasse 23, Vienna, 1090, Austria
                [7 ]Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University, 20 Duke Medicine Cir, Durham, NC 27710, USA
                [8 ]MSD China, Plot B-12, Electronic City West Zone, Chaoyang District, Beijing, 100012, China
                [9 ]Merck & Co., Inc., 90 E Scott Ave, Rahway, NJ 07065, USA
                Article
                DOI: 10.2217/fon-2022-0776
                PubMed ID: 36705526
                SO-VID: 4b52e522-4022-4d3f-9355-8d8954b42065
                Copyright © © 2022
                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content758

                See all similar

                Cited by4

                See all cited by

                Most referenced authors701

                See all reference authors