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2. Gene-expression-based T-Cell-to-Stroma Enrichment (TSE) score predicts response to immune checkpoint inhibitors in urothelial cancer

Author

Rijnders, Maud, Nakauma-González, J. Alberto, Robbrecht, Debbie G. J., Gil-Jimenez, Alberto, Balcioglu, Hayri E., Oostvogels, Astrid A. M., Aarts, Maureen J. B., Boormans, Joost L., Hamberg, Paul, van der Heijden, Michiel S., Szabados, Bernadett E., van Leenders, Geert J. L. H., Mehra, Niven, Voortman, Jens, Westgeest, Hans M., de Wit, Ronald, van der Veldt, Astrid A. M., Debets, Reno, and Lolkema, Martijn P.

Published
2024
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4. Genomic and transcriptomic features of androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer

Author

Zhu, Xiaolin, Farsh, Tatyanah, Vis, Daniel, Yu, Ivan, Li, Haolong, Liu, Tianyi, Sjostrom, Martin, Shrestha, Raunak, Kneppers, Jeroen, Severson, Tesa, Zhang, Meng, Lundberg, Arian, Rodriguez, Thaidy Moreno, Weinstein, Alana S., Foye, Adam, Mehra, Niven, Aggarwal, Rahul R., Bergman, Andries M., Small, Eric J., Lack, Nathan A., Zwart, Wilbert, Quigley, David A., van der Heijden, Michiel S., and Feng, Felix Y.

Subjects
Oncology, Experimental, Prostate cancer -- Development and progression -- Genetic aspects -- Drug therapy, Metastasis -- Development and progression -- Genetic aspects -- Drug therapy, Drug resistance -- Genetic aspects, Cellular signal transduction -- Research, Genetic transcription -- Research, Cancer -- Research, Health care industry
Abstract

BACKGROUND. Androgen receptor signaling inhibitors (ARSIs) have improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), but their clinical benefit is limited by treatment resistance. METHODS. To investigate the mechanisms of ARSI resistance, we analyzed the whole-genome (n = 45) and transcriptome (n = 31) sequencing data generated from paired metastatic biopsies obtained before initiation of first-line ARSI therapy for mCRPC and after radiographic disease progression. We investigated the effects of genetic and pharmacologic modulation of SSTR1 in 22Rv1 cells, a representative mCRPC cell line. RESULTS. We confirmed the predominant role of tumor genetic alterations converging on augmenting androgen receptor (AR) signaling and the increased transcriptional heterogeneity and lineage plasticity during the emergence of ARSI resistance. We further identified amplifications involving a putative enhancer downstream of the AR and transcriptional downregulation of SSTR1, encoding somatostatin receptor 1, in ARSI-resistant tumors. We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA- approved drug pasireotide suppressed 22Rv1 cell proliferation. CONCLUSION. Our findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes. FUNDING. National Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute., Introduction Metastatic castration-resistant prostate cancer (mCRPC) is the lethal form of prostate cancer (PCa) (1). Androgen receptor signaling inhibitors (ARSIs), such as abiraterone and enzalutamide, have improved outcomes for patients [...]

Published
2024
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8. Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy

Author

Rosenberg, Jonathan E., Mamtani, Ronac, Sonpavde, Guru P., Loriot, Yohann, Duran, Ignacio, Lee, Jae-Lyun, Matsubara, Nobuaki, Vulsteke, Christof, Castellano, Daniel, Sridhar, Srikala S., Pappot, Helle, Gurney, Howard, Bedke, Jens, van der Heijden, Michiel S., Galli, Luca, Keam, Bhumsuk, Masumori, Naoya, Meran, Johannes, O'Donnell, Peter H., Park, Se Hoon, Grande, Enrique, Sengeløv, Lisa, Uemura, Hiroji, Skaltsa, Konstantina, Campbell, Mary, Matsangou, Maria, Wu, Chunzhang, Hepp, Zsolt, McKay, Caroline, Powles, Thomas, and Petrylak, Daniel P.

Published
2024
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9. Management of Lymph Node–positive Penile Cancer: A Systematic Review

Author

Sachdeva, Ashwin, McGuinness, Luke, Zapala, Łukasz, Greco, Isabella, Garcia-Perdomo, Herney Andres, Kailavasan, Mithun, Antunes-Lopes, Tiago, Ayres, Benjamin, Barreto, Lenka, Campi, Riccardo, Crook, Juanita, Johnstone, Peter, Kumar, Vivek, Manzie, Kenneth, Marcus, Jack David, Necchi, Andrea, Oliveira, Pedro, Osborne, John, Pagliaro, Lance C., Protzel, Chris, Bryan Rumble, R., Sánchez Martínez, Diego F., Spiess, Philippe E., Tagawa, Scott T., van der Heijden, Michiel S., Parnham, Arie S., Pettaway, Curtis A., Albersen, Maarten, Sangar, Vijay K., Brouwer, Oscar R., and Sakalis, Vasileios I.

Published
2024
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10. Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial

Author

van der Heijden, Michiel S, Powles, Thomas, Petrylak, Daniel, de Wit, Ronald, Necchi, Andrea, Sternberg, Cora N, Matsubara, Nobuaki, Nishiyama, Hiroyuki, Castellano, Daniel, Hussain, Syed A, Bamias, Aristotelis, Gakis, Georgios, Lee, Jae-Lyun, Tagawa, Scott T, Vaishampayan, Ulka, Aragon-Ching, Jeanny B, Eigl, Bernie J, Hozak, Rebecca R, Rasmussen, Erik R, Xia, Meng Summer, Rhodes, Ryan, Wijayawardana, Sameera, Bell-McGuinn, Katherine M, Aggarwal, Amit, and Drakaki, Alexandra

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Genetic Testing, Cancer, Genetics, Good Health and Well Being, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Biomarkers, Biomarkers, Tumor, Carcinoma, Transitional Cell, Humans, Urinary Bladder Neoplasms
Abstract

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab.

Published
2022

11. FGFR Inhibition in Urothelial Carcinoma

Author

Li, Roger, Linscott, Joshua, Catto, James W.F., Daneshmand, Siamak, Faltas, Bishoy M., Kamat, Ashish M., Meeks, Joshua J., Necchi, Andrea, Pradere, Benjamin, Ross, Jeffrey S., van der Heijden, Michiel S., van Rhijn, Bas W.G., and Loriot, Yohann

Published
2024
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12. Disease-Free Survival of Patients With Muscle-Invasive Bladder Cancer Treated With Radical Cystectomy Versus Bladder-Preserving Therapy: A Nationwide Study

Author

Brück, Katharina, Meijer, Richard P., Boormans, Joost L., Kiemeney, Lambertus A., Witjes, J. Alfred, van Hoogstraten, Lisa M.C., van der Heijden, Michiel S., Donders, A. Rogier, Franckena, Martine, Uyl de Groot, Carin A., Leliveld, Annemarie M., Aben, Katja K.H., and Hulshof, Maarten C.C.M.

Published
2024
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13. High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Author

van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B. M., Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L., Hackinger, Sophie, Braaf, Linde M., Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W., Hendricksen, Kees, de Feijter, Jeantine M., Boellaard, Thierry N., Meijer, Richard P., van der Heijden, Antoine G., Rosenfeld, Nitzan, van Rhijn, Bas W. G., Jones, Greg, and van der Heijden, Michiel S.

Published
2023
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14. Author Correction: High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial

Author

van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B. M., Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L., Hackinger, Sophie, Braaf, Linde M., Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W., Hendricksen, Kees, de Feijter, Jeantine M., Boellaard, Thierry N., Meijer, Richard P., van der Heijden, Antoine G., Rosenfeld, Nitzan, van Rhijn, Bas W. G., Jones, Greg, and van der Heijden, Michiel S.

Published
2024
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15. Publisher Correction: Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

Author

Powles, Thomas, Kockx, Mark, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Szabados, Bernadett, Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez, Maria Jose, Suarez, Cristina, Linch, Mark, Prendergast, Aaron, van Dam, Pieter-Jan, Stanoeva, Diana, Daelemans, Sofie, Mariathasan, Sanjeev, Tea, Joy S., Mousa, Kelly, Banchereau, Romain, and Castellano, Daniel

Published
2023
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16. European Association of Urology-American Society of Clinical Oncology Collaborative Guideline on Penile Cancer: 2023 Update

Author

Brouwer, Oscar R., Albersen, Maarten, Parnham, Arie, Protzel, Chris, Pettaway, Curtis A., Ayres, Benjamin, Antunes-Lopes, Tiago, Barreto, Lenka, Campi, Riccardo, Crook, Juanita, Fernández-Pello, Sergio, Greco, Isabella, van der Heijden, Michiel S., Johnstone, Peter A.S., Kailavasan, Mithun, Manzie, Kenneth, Marcus, Jack David, Necchi, Andrea, Oliveira, Pedro, Osborne, John, Pagliaro, Lance C., Garcia-Perdomo, Herney A., Rumble, R. Bryan, Sachdeva, Ashwin, Sakalis, Vasileios I., Zapala, Łukasz, Sánchez Martínez, Diego F., Spiess, Philippe E., and Tagawa, Scott T.

Published
2023
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17. Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis

Author

de Jong, Joep J, Liu, Yang, Robertson, A Gordon, Seiler, Roland, Groeneveld, Clarice S, van der Heijden, Michiel S, Wright, Jonathan L, Douglas, James, Dall’Era, Marc, Crabb, Simon J, van Rhijn, Bas WG, van Kessel, Kim EM, Davicioni, Elai, Castro, Mauro AA, Lotan, Yair, Zwarthoff, Ellen C, Black, Peter C, Boormans, Joost L, and Gibb, Ewan A

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biotechnology, Cancer, Human Genome, Urologic Diseases, Genetics, Good Health and Well Being, Aged, Biomarkers, Tumor, Carcinoma, Papillary, Combined Modality Therapy, Cystectomy, Female, Follow-Up Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Muscle Neoplasms, Neoadjuvant Therapy, Prognosis, RNA, Long Noncoding, Retrospective Studies, Survival Rate, Urinary Bladder Neoplasms, Gene expression analysis, Long non-coding RNA, Molecular subtypes, Muscle-invasive bladder cancer, Clinical Sciences
Abstract

BACKGROUND:Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution. METHODS:LncRNA expression was quantified from microarray data of a MIBC cohort treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) (n = 223). Unsupervised consensus clustering of highly variant lncRNAs identified a four-cluster solution, which was characterized using a panel of MIBC biomarkers, regulon activity profiles, gene signatures, and survival analysis. The four-cluster solution was confirmed in The Cancer Genome Atlas (TCGA) cohort (n = 405). A single-sample genomic classifier (GC) was trained using ridge-penalized logistic regression and validated in two independent cohorts (n = 255 and n = 94). RESULTS:NAC and TCGA cohorts both contained an lncRNA cluster (LC3) with favorable prognosis that was enriched with tumors of the luminal-papillary (LP) subtype. In both cohorts, patients with LP tumors in LC3 (LPL-C3) were younger and had organ-confined, node-negative disease. The LPL-C3 tumors had enhanced FGFR3, SHH, and wild-type p53 pathway activity. In the TCGA cohort, LPL-C3 tumors were enriched for FGFR3 mutations and depleted for TP53 and RB1 mutations. A GC trained to identify these LPL-C3 patients showed robust performance in two validation cohorts. CONCLUSIONS:Using lncRNA expression profiles, we identified a biologically distinct subgroup of luminal-papillary MIBC with a favorable prognosis. These data suggest that lncRNAs provide additional information for higher-resolution subtyping, potentially improving precision patient management.

Published
2019

18. The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact.

Author

van Dessel, Lisanne F, van Riet, Job, Smits, Minke, Zhu, Yanyun, Hamberg, Paul, van der Heijden, Michiel S, Bergman, Andries M, van Oort, Inge M, de Wit, Ronald, Voest, Emile E, Steeghs, Neeltje, Yamaguchi, Takafumi N, Livingstone, Julie, Boutros, Paul C, Martens, John WM, Sleijfer, Stefan, Cuppen, Edwin, Zwart, Wilbert, van de Werken, Harmen JG, Mehra, Niven, and Lolkema, Martijn P

Subjects
Lymph Nodes, Humans, Bone Neoplasms, Liver Neoplasms, Soft Tissue Neoplasms, Prostatic Neoplasms, Neoplasm Metastasis, Cyclin-Dependent Kinases, Oncogene Proteins, Fusion, BRCA2 Protein, Receptors, Androgen, Genotype, Male, Microsatellite Instability, Enhancer Elements, Genetic, DNA Copy Number Variations, Recombinational DNA Repair, Prostatic Neoplasms, Castration-Resistant, Whole Genome Sequencing, Chromatin Immunoprecipitation Sequencing, Oncogene Proteins, Fusion, Receptors, Androgen, Enhancer Elements, Genetic, Castration-Resistant, Biotechnology, Genetics, Cancer, Prostate Cancer, Urologic Diseases, Human Genome
Abstract

Metastatic castration-resistant prostate cancer (mCRPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. Here we present the whole-genome sequencing (WGS) analysis of fresh-frozen metastatic biopsies from 197 mCRPC patients. Using unsupervised clustering based on genomic features, we define eight distinct genomic clusters. We observe potentially clinically relevant genotypes, including microsatellite instability (MSI), homologous recombination deficiency (HRD) enriched with genomic deletions and BRCA2 aberrations, a tandem duplication genotype associated with CDK12-/- and a chromothripsis-enriched subgroup. Our data suggests that stratification on WGS characteristics may improve identification of MSI, CDK12-/- and HRD patients. From WGS and ChIP-seq data, we show the potential relevance of recurrent alterations in non-coding regions identified with WGS and highlight the central role of AR signaling in tumor progression. These data underline the potential value of using WGS to accurately stratify mCRPC patients into clinically actionable subgroups.

Published
2019

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

Park, Se Hoon, van der Heijden, Michiel S., Necchi, Andrea, Castellano, Daniel, Bamias, Aristotelis, Lee, Jae Lyun, De Giorgi, Ugo, Bögemann, Martin, Eigl, Bernhard J., Tsiatas, Marinos, Powles, Thomas, Novikov, Andrey, Skoneczna, Iwona, Mukherjee, Som D., Suarez, Cristina, Westgeest, Hans, Fradet, Yves, Flechon, Aude, Ou, Yen-Chuan, Park, Inkeun, Matveev, Vsevolod, Pérez-Valderrama, Begoña, Cheng, Susanna, Frank, Stephen, Gurney, Howard, Anido, Urbano, Hamzaj, Alketa, Retz, Margitta, Sridhar, Srikala, Scagliotti, Giorgio Vittorio, Voortman, Jens, Alekseev, Boris, Alyasova, Anna, Komyakov, Boris, Dumez, Herlinde, Pavic, Michel, Kimura, Go, Mizokami, Atsushi, Osanto, Susanne, Arranz, Jose Angel, Piersma, Djura, Shin, Sang Joon, Karyakin, Oleg, Delgado, Ignacio, Gonzalez, Jose Luis, Pang, See-Tong, Tran, Anna, Lipatov, Oleg, Su, Wen-Pin, Flaig, Thomas, Alva, Ajjai, Park Kyong, Hwa, Kopyltsov, Evgeny, Almagro, Elena, Domenech, Monserrat, Chang, Yen-Hwa, Sautois, Brieuc, Ravaux, Andre, Aravantinos, Gerasimos, Georgoulias, Vasileios, Mulder, Sasja, Kim, Yu Jung, Kater, Fabio, Chevreau, Christine, Tagawa, Scott, Zalewski, Pawel, Joly, Florence, Loriot, Yohann, Hatiboglu, Gencay, Gianni, Luca, Morelli, Franco, Tambaro, Rosa, Hashimoto, Yasuhiro, Nosov, Alexander, Font, Albert, Rodriguez-Vida, Alejo M., Jones, Robert, Vasudev, Naveen, Srinivas, Sandhya, Zhang, Jingsong, Gil, Thierry, Finch, Daygen, Grimm, Marc-Oliver, Su, Yu-Li, Chowdhury, Simon, Hocking, Christopher, Plas, Eugen, North, Scott, Jensen, Niels Viggo, Theodore, Christine, Imkamp, Florian, Peer, Avivit, Kobayashi, Takashi, Sakai, Hideki, Sassa, Naoto, Yoshimura, Kazuhiro, Aarts, Maureen, Ferreira Castro, Ana, Topuzov, Marlen, Rodriguez, Juan Francisco, Vazquez, Federico Jose, Tsai, Yu-Chieh, Crabb, Simon, Hussain, Syed, Bendell, Johanna, Gross-Goupil, Marine, Gwenaelle, Gravis, Berger, Raanan, Statsenko, Galina, Evans, Linda, Drakaki, Alexandra, Somer, Bradley, Davis, Ian, Lynam, James, Borges, Giuliano, Dettino, Aldo, Fay, André P., Martins, Graziella, Zucca, Luis Eduardo, Agerbaek, Mads, Kalofonos, Haralambos, Rosenbaum, Eli, Enokida, Hideki, Kikukawa, Hiroaki, Nishimura, Kazuo, Tamada, Satoshi, Uemura, Motohide, Lopez, Yamil, Gietema, Jourik, Slojewski, Marcin, Fernandes, Isabel, Smolin, Alexey, Mazhar, Danish, Kalebasty, Arash Rezazadeh, Carthon, Bradley, Loidl, Wolfgang, Franke, Fabio, Girotto, Gustavo, Alimohamed, Nimira, Macfarlane, Robyn, Pappot, Helle, Niegisch, Guenter, Mavroudis, Dimitrios, Sella, Avishay, Porta, Camillo, Ebara, Shin, Nakamura, Motonobu, Obara, Wataru, Okuno, Norihiko, Shinohara, Nobuo, Sugimoto, Mikio, Suzuki, Akitaka, Tokuda, Noriaki, Uemura, Hiroji, Yamaguchi, Akito, Ramirez, Francisco, Rozanowski, Pawel, Wiechno, Pawel, Keam, Bhumsuk, Kislov, Nikolay, Plaksin, Denis, Cicin, Irfan, Kumar, Satish, Galsky, Matthew D., Petrylak, Daniel P., Rosales, Joseph, Vaishampayan, Ulka, Culine, Stephane, Papandreou, Christos, Nara, Taketoshi, Erman, Mustafa, Kreiger, Laurence, Janoski, Juliana, Rosa, Diogo, Siqueira, Mariana, Canil, Christina, Sengelov, Lisa, Tourani, Jean-Marc, Arai, Gaku, Hashine, Katsuyoshi, Kawakita, Mutsushi, Nakaigawa, Noboru, Nomi, Hayahito, Shiina, Hiroaki, Suzuki, Hiroyoshi, Yonese, Junji, Kuri, Roberto, Macedo, Eleazar, Rivera, Samuel, Villalobos Prieto, Alberto, Polakiewicz-Gilowska, Anna, Zaucha, Renata, Lopes, Fabio, Ponomarev, Roman, Pomerantz, Mark, Shariat, Shahrokh, Luk, Cynthia, Lesniewski-Kmak, Krzysztof, van der Heijden, Michiel S, Galsky, Matthew D, Petrylak, Daniel P, Ogawa, Osamu, Lee, Jae-Lyun, Eigl, Bernhard J, Mukherjee, Som D, Suárez, Cristina, Fay, André P, Duran, Ignacio, Wildsmith, Sophie, He, Philip, Angra, Natasha, Gupta, Ashok K, Levin, Wendy, and Bellmunt, Joaquim

Published
2020
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20. Final Results of Neoadjuvant Atezolizumab in Cisplatin-ineligible Patients with Muscle-invasive Urothelial Cancer of the Bladder

Author

Szabados, Bernadett, Kockx, Mark, Assaf, Zoe June, van Dam, Pieter-Jan, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez, Maria Jose, Suarez, Cristina, Linch, Mark, Prendergast, Aaron, Tyson, Charlotte, Stanoeva, Diana, Daelemans, Sofie, Rombouts, Miche, Mariathasan, Sanjeev, Tea, Joy S., Mousa, Kelly, Sharma, Shruti, Aleshin, Alexey, Banchereau, Romain, Castellano, Daniel, and Powles, Thomas

Published
2022
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22. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.

Author

Mariathasan, Sanjeev, Turley, Shannon J, Nickles, Dorothee, Castiglioni, Alessandra, Yuen, Kobe, Wang, Yulei, Kadel, Edward E, Koeppen, Hartmut, Astarita, Jillian L, Cubas, Rafael, Jhunjhunwala, Suchit, Banchereau, Romain, Yang, Yagai, Guan, Yinghui, Chalouni, Cecile, Ziai, James, Şenbabaoğlu, Yasin, Santoro, Stephen, Sheinson, Daniel, Hung, Jeffrey, Giltnane, Jennifer M, Pierce, Andrew A, Mesh, Kathryn, Lianoglou, Steve, Riegler, Johannes, Carano, Richard AD, Eriksson, Pontus, Höglund, Mattias, Somarriba, Loan, Halligan, Daniel L, van der Heijden, Michiel S, Loriot, Yohann, Rosenberg, Jonathan E, Fong, Lawrence, Mellman, Ira, Chen, Daniel S, Green, Marjorie, Derleth, Christina, Fine, Gregg D, Hegde, Priti S, Bourgon, Richard, and Powles, Thomas

Subjects
Urothelium, CD8-Positive T-Lymphocytes, Fibroblasts, Animals, Humans, Mice, Urologic Neoplasms, Neoplasm Metastasis, Disease Models, Animal, Collagen, Transforming Growth Factor beta, Antibodies, Antibodies, Monoclonal, Antigens, Neoplasm, Treatment Outcome, Immunotherapy, Cohort Studies, Signal Transduction, Drug Resistance, Neoplasm, Phenotype, Mutation, Tumor Microenvironment, Antibodies, Monoclonal, Humanized, Cell Cycle Checkpoints, B7-H1 Antigen, Monoclonal, Humanized, Antigens, Neoplasm, Disease Models, Animal, Drug Resistance, General Science & Technology
Abstract

Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.

Published
2018

23. PD34-11 NIVOLUMAB PLUS GEMCITABINE-CISPLATIN VERSUS GEMCITABINE-CISPLATIN ALONE IN PATIENTS WITH PREVIOUSLY UNTREATED UNRESECTABLE OR METASTATIC UROTHELIAL CARCINOMA: RESULTS OF ANALYSES TO CHARACTERIZE BENEFIT IN RESPONDERS FROM THE PHASE 3 CHECKMATE 901 TRIAL

Author

Sonpavde, Guru, primary, van der Heijden, Michiel S., additional, Powles, Thomas, additional, Necchi, Andrea, additional, Burotto, Mauricio, additional, Schenker, Michael, additional, Sade, Juan Pablo, additional, Bamias, Aristotelis, additional, Beuzeboc, Philippe, additional, Bedke, Jens, additional, Oldenburg, Jan, additional, Ürün, Yüksel, additional, Ye, Dingwei, additional, Valderrama, Begoña P., additional, Tomita, Yoshihiko, additional, Filian, Jeiry, additional, Wang, Lily, additional, Purcea, Daniela, additional, Nasroulah, Federico, additional, and Galsky, Matthew D., additional

Published
2024
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24. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer

Author

Powles, Thomas, primary, Valderrama, Begoña P., additional, Gupta, Shilpa, additional, Bedke, Jens, additional, Kikuchi, Eiji, additional, Hoffman-Censits, Jean, additional, Iyer, Gopa, additional, Vulsteke, Christof, additional, Park, Se Hoon, additional, Shin, Sang Joon, additional, Castellano, Daniel, additional, Fornarini, Giuseppe, additional, Li, Jian-Ri, additional, Gümüş, Mahmut, additional, Mar, Nataliya, additional, Loriot, Yohann, additional, Fléchon, Aude, additional, Duran, Ignacio, additional, Drakaki, Alexandra, additional, Narayanan, Sujata, additional, Yu, Xuesong, additional, Gorla, Seema, additional, Homet Moreno, Blanca, additional, and van der Heijden, Michiel S., additional

Published
2024
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25. Partial Response and Stable Disease Correlate with Positive Outcomes in Atezolizumab-treated Patients with Advanced Urinary Tract Carcinoma

Author

Bedke, Jens, Merseburger, Axel S., Loriot, Yohann, Castellano, Daniel, Choy, Ernest, Duran, Ignacio, Rosenberg, Jonathan E., Petrylak, Daniel P., Dreicer, Robert, Perez-Gracia, Jose L., Hoffman-Censits, Jean H., Van Der Heijden, Michiel S., Pavlova, Julie, Thiebach, Lars, de Ducla, Sabine, Fear, Simon, Powles, Thomas, and Sternberg, Cora N.

Published
2021
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26. Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial

Author

Szabados, Bernadett, Rodriguez-Vida, Alejo, Durán, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., Pous, Albert Font, Gravis, Gwenaelle, Herranz, Urbano Anido, Protheroe, Andrew, Ravaud, Alain, Maillet, Denis, Mendez-Vidal, Maria J., Suárez, Cristina, Linch, Mark, Prendergast, Aaron, Tyson, Charlotte, Mousa, Kelly, Castellano, Daniel, and Powles, Thomas

Published
2021
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27. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial

Author

Yu, Evan Y, Petrylak, Daniel P, O'Donnell, Peter H, Lee, Jae-Lyun, van der Heijden, Michiel S, Loriot, Yohann, Stein, Mark N, Necchi, Andrea, Kojima, Takahiro, Harrison, Michael R, Hoon Park, Se, Quinn, David I, Heath, Elisabeth I, Rosenberg, Jonathan E, Steinberg, Joyce, Liang, Shang-Ying, Trowbridge, Janet, Campbell, Mary, McGregor, Bradley, and Balar, Arjun V

Published
2021
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28. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial

Author

Bellmunt, Joaquim, Hussain, Maha, Gschwend, Jürgen E, Albers, Peter, Oudard, Stephane, Castellano, Daniel, Daneshmand, Siamak, Nishiyama, Hiroyuki, Majchrowicz, Martin, Degaonkar, Viraj, Shi, Yi, Mariathasan, Sanjeev, Grivas, Petros, Drakaki, Alexandra, O'Donnell, Peter H, Rosenberg, Jonathan E, Geynisman, Daniel M, Petrylak, Daniel P, Hoffman-Censits, Jean, Bedke, Jens, Kalebasty, Arash Rezazadeh, Zakharia, Yousef, van der Heijden, Michiel S, Sternberg, Cora N, Davarpanah, Nicole N, and Powles, Thomas

Published
2021
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29. Author Correction: High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial (Nature Medicine, (2023), 29, 3, (588-592), 10.1038/s41591-022-02199-y)

Author

Cancer, MS Medische Oncologie, MS Urologische Oncologie, van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B M, Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L, Hackinger, Sophie, Braaf, Linde M, Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W, Hendricksen, Kees, de Feijter, Jeantine M, Boellaard, Thierry N, Meijer, Richard P, van der Heijden, Antoine G, Rosenfeld, Nitzan, van Rhijn, Bas W G, Jones, Greg, van der Heijden, Michiel S, Cancer, MS Medische Oncologie, MS Urologische Oncologie, van Dorp, Jeroen, Pipinikas, Christodoulos, Suelmann, Britt B M, Mehra, Niven, van Dijk, Nick, Marsico, Giovanni, van Montfoort, Maurits L, Hackinger, Sophie, Braaf, Linde M, Amarante, Tauanne, van Steenis, Charlaine, McLay, Kirsten, Daletzakis, Antonios, van den Broek, Daan, van de Kamp, Maaike W, Hendricksen, Kees, de Feijter, Jeantine M, Boellaard, Thierry N, Meijer, Richard P, van der Heijden, Antoine G, Rosenfeld, Nitzan, van Rhijn, Bas W G, Jones, Greg, and van der Heijden, Michiel S

Published
2024

30. Urine-derived bladder cancer organoids (urinoids) as a tool for cancer longitudinal response monitoring and therapy adaptation

Author

Cancer, MS Urologische Oncologie, Pathologie Pathologen staf, Hubrecht Institute with UMC, Viergever, Bastiaan J, Raats, Daniëlle A E, Geurts, Veerle, Mullenders, Jasper, Jonges, Trudy N, van der Heijden, Michiel S, van Es, Johan H, Kranenburg, Onno, Meijer, Richard P, Cancer, MS Urologische Oncologie, Pathologie Pathologen staf, Hubrecht Institute with UMC, Viergever, Bastiaan J, Raats, Daniëlle A E, Geurts, Veerle, Mullenders, Jasper, Jonges, Trudy N, van der Heijden, Michiel S, van Es, Johan H, Kranenburg, Onno, and Meijer, Richard P

Published
2024

31. Treatment patterns and survival outcomes of patients admitted to the intensive care unit due to immune‐related adverse events of immune checkpoint inhibitors.

Author

Lin, Lishi, Houwink, Aletta P. I., van Dieren, Jolanda M., Wolthuis, Esther K., van Thienen, Johannes V., van der Heijden, Michiel S., Haanen, John B. A. G., Beijnen, Jos H., and Huitema, Alwin D. R.

Subjects
DRUG side effects, IMMUNE checkpoint inhibitors, INTENSIVE care patients, SURVIVAL rate, OVERALL survival
Abstract

Introduction: Severe immune‐related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective study, we determined the incidence, treatment patterns and survival outcomes of this patient population at a comprehensive cancer center. Methods: All patients admitted to the ICU due to irAEs from ICI treatment between January 2015 and July 2022 were included. Descriptive statistics were reported on patient characteristics and treatment patterns during hospital admission. Overall survival (OS) from the time of ICU discharge to death was estimated using the Kaplan–Meier method. Results: Over the study period, 5561 patients received at least one ICI administration, of which 32 patients (0.6%) were admitted to the ICU due to irAEs. Twenty patients were treated with anti‐PD‐1 plus anti‐CTLA‐4 treatment, whereas 12 patients were treated with ICI monotherapy. The type of irAEs were de novo diabetes‐related ketoacidosis (n = 8), immune‐related gastrointestinal toxicity (n = 8), myocarditis or myositis (n = 10), nephritis (n = 3), pneumonitis (n = 2), and myelitis (n = 1). The median duration of ICU admission was 3 days (interquartile range: 2–6 days). Three patients died during ICU admission. The median OS of the patients who were discharged from the ICU was 18 months (95% confidence interval, 5.0—NA). Conclusion: The incidence of irAEs leading to ICU admission in patients treated with ICI was low in this study. ICU mortality due to irAEs was low and a subset of this patient population even had long‐term survival. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Author

Wong, Suet-Lai Shirley, Tan, Thean Hsiang, Hovey, Elizabeth Jane, Clay, Timothy Dudley, Wan Ng, Siobhan Su, Rutten, Annemie, Machiels, Jean-Pascal, Dumez, Herlinde, Cheng, Susanna Yee-Shan, Ferrario, Cristiano, Sengeloev, Lisa, Jensen, Niels Viggo, Thibault, Constance, Laguerre, Brigitte, Joly, Florence, Culine, Stéphane, Becht, Catherine, Niegisch, Günter, Stöckle, Michael, Grimm, Marc-Oliver, Schwentner, Christina A, Schultze-Seemann, Wolfgang, Kalofonos, Haralambos, Mavroudis, Dimitrios, Papandreou, Christos, Karavasilis, Vasilis, Révész, Janos, Rosenbaum, Eli, Leibowitz-Amit, Raya, Kejzman, Daniel, Sarid, David, Scagliotti, Giorgio Vittorio, Bracarda, Sergio, Massari, Francesco, Osawa, Takahiro, Miyajima, Naoto, Shinohara, Nobuo, Fukuta, Fumimasa, Ohyama, Chikara, Obara, Wataru, Yamashita, Shinichi, Tomita, Yoshihiko, Kawai, Koji, Fukasawa, Satoshi, Oyama, Masafumi, Yonese, Junji, Nagata, Masayoshi, Uemura, Motohide, Nishimura, Kazuo, Kawakita, Mutsushi, Tsunemori, Hiroyuki, Hashine, Katsuyoshi, Inokuchi, Junichi, Yokomizo, Akira, Nagamori, Satoshi, Lee, Hyo Jin, Park, Se Hoon, Rha, Sun Young, Kim, Yu Jung, Lee, Yun-Gyoo, Vazquez Cortés, Leticia, Lorena Urzua Flores, Claudia, Blaisse, Reinoud J.B., Erdkamp, Fransiscus L.G., Aarts, Maureen J.B., Wojcik-Tomaszewska, Joanna, Tomczak, Piotr, Sikora-Kupis, Bozena, Schenker, Michael, Herzal, Alina Amalia, Udrea, Anghel Adrian, Karlov, Petr, Fomkin, Roman, Gajate Borau, Pablo, Grande, Enrique, Delgado Mignorance, Juan Ignacio, Su, Yu-Li, Li, Jian-Ri, Lin, Chien-Liang, Lin, Chia-Chi, Yeh, Su-Peng, Erman, Mustafa, Urun, Yuksel, Golovko, Yuriy, Bondarenko, Igor, Sinielnikov, Ivan, Crabb, Simon J., Syndikus, Isabel, Huddart, Robert, Sundar, Santhanam, Chowdhury, Simon, Sarwar, Naveed, Flaig, Thomas W., Pan, Chong Xian, Schwarz, James K., Cultrera, Jennifer Lyn, Acs, Peter Istvan, Hainsworth, John D., Herms, Benjamin T., Lawler, William Eyre, Lowe, Thomas Eugene, Petrylak, Daniel P, de Wit, Ronald, Chi, Kim N, Drakaki, Alexandra, Sternberg, Cora N, Nishiyama, Hiroyuki, Castellano, Daniel, Hussain, Syed A, Fléchon, Aude, Bamias, Aristotelis, Yu, Evan Y, van der Heijden, Michiel S, Matsubara, Nobuaki, Alekseev, Boris, Necchi, Andrea, Géczi, Lajos, Ou, Yen-Chuan, Coskun, Hasan Senol, Su, Wen-Pin, Bedke, Jens, Gakis, Georgios, Percent, Ivor J, Lee, Jae-Lyun, Tucci, Marcello, Semenov, Andrey, Laestadius, Fredrik, Peer, Avivit, Tortora, Giampaolo, Safina, Sufia, Garcia del Muro, Xavier, Rodriguez-Vida, Alejo, Cicin, Irfan, Harputluoglu, Hakan, Tagawa, Scott T, Vaishampayan, Ulka, Aragon-Ching, Jeanny B, Hamid, Oday, Liepa, Astra M, Wijayawardana, Sameera, Russo, Francesca, Walgren, Richard A, Zimmermann, Annamaria H, Hozak, Rebecca R, Bell-McGuinn, Katherine M, and Powles, Thomas

Published
2020
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34. Reply to Y.-N. Feng et al

Author

de Vries, Hielke M., primary, Brouwer, Oscar R., additional, Schaake, Eva, additional, and van der Heijden, Michiel S., additional

Published
2024
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37. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial

Author

van Dijk, Nick, Gil-Jimenez, Alberto, Silina, Karina, Hendricksen, Kees, Smit, Laura A., de Feijter, Jeantine M., van Montfoort, Maurits L., van Rooijen, Charlotte, Peters, Dennis, Broeks, Annegien, van der Poel, Henk G., Bruining, Annemarie, Lubeck, Yoni, Sikorska, Karolina, Boellaard, Thierry N., Kvistborg, Pia, Vis, Daniel J., Hooijberg, Erik, Schumacher, Ton N., van den Broek, Maries, Wessels, Lodewyk F. A., Blank, Christian U., van Rhijn, Bas W., and van der Heijden, Michiel S.

Published
2020
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39. High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade

Author

Yuen, Kobe C., Liu, Li-Fen, Gupta, Vinita, Madireddi, Shravan, Keerthivasan, Shilpa, Li, Congfen, Rishipathak, Deepali, Williams, Patrick, Kadel, Edward E., III, Koeppen, Harmut, Chen, Ying-Jiun, Modrusan, Zora, Grogan, Jane L., Banchereau, Romain, Leng, Ning, Thastrom, Ann Christine, Shen, Xiadong, Hashimoto, Kenji, Tayama, Darren, van der Heijden, Michiel S., Rosenberg, Jonathan E., McDermott, David F., Powles, Thomas, Hegde, Priti S., Huseni, Mahrukh A., and Mariathasan, Sanjeev

Subjects
Interleukin-8 -- Health aspects, Metastasis -- Drug therapy -- Patient outcomes, Bladder cancer -- Drug therapy -- Patient outcomes, Apoptotic proteins -- Health aspects, Carcinoma, Renal cell -- Drug therapy -- Patient outcomes, Monoclonal antibodies -- Patient outcomes -- Health aspects, Biological sciences, Health
Abstract

Although elevated plasma interleukin-8 (pIL-8) has been associated with poor outcome to immune checkpoint blockade.sup.1, this has not been comprehensively evaluated in large randomized studies. Here we analyzed circulating pIL-8 and IL8 gene expression in peripheral blood mononuclear cells and tumors of patients treated with atezolizumab (anti-PD-L1 monoclonal antibody) from multiple randomized trials representing 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma. High levels of IL-8 in plasma, peripheral blood mononuclear cells and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metastatic renal cell carcinoma, even in tumors that were classically CD8.sup.+ T cell inflamed. Low baseline pIL-8 in patients with mUC was associated with increased response to atezolizumab and chemotherapy. Patients with mUC who experienced on-treatment decreases in pIL-8 exhibited improved overall survival when treated with atezolizumab but not with chemotherapy. Single-cell RNA sequencing of the immune compartment showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and that high IL8 expression is associated with downregulation of the antigen-presentation machinery. Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation will be essential for improving outcomes of patients treated with immune checkpoint inhibitors. In a retrospective analysis of data from three clinical trials, increased baseline peripheral and tumor IL-8 levels were associated with worse clinical outcomes in patients with metastatic urothelial carcinoma and metastatic renal cell carcinoma treated with anti-PD-L1 therapy., Author(s): Kobe C. Yuen [sup.1] , Li-Fen Liu [sup.1] , Vinita Gupta [sup.1] , Shravan Madireddi [sup.1] , Shilpa Keerthivasan [sup.1] , Congfen Li [sup.1] , Deepali Rishipathak [sup.1] , [...]

Published
2020
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42. Nivolumab plus Gemcitabine–Cisplatin in Advanced Urothelial Carcinoma

Author

van der Heijden, Michiel S., primary, Sonpavde, Guru, additional, Powles, Thomas, additional, Necchi, Andrea, additional, Burotto, Mauricio, additional, Schenker, Michael, additional, Sade, Juan Pablo, additional, Bamias, Aristotelis, additional, Beuzeboc, Philippe, additional, Bedke, Jens, additional, Oldenburg, Jan, additional, Chatta, Gurkamal, additional, Ürün, Yüksel, additional, Ye, Dingwei, additional, He, Zhisong, additional, Valderrama, Begoña P., additional, Ku, Ja Hyeon, additional, Tomita, Yoshihiko, additional, Filian, Jeiry, additional, Wang, Lily, additional, Purcea, Daniela, additional, Patel, Miraj Y., additional, Nasroulah, Federico, additional, and Galsky, Matthew D., additional

Published
2023
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43. Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial

Author

de Vries, Hielke M., primary, Rafael, Tynisha S., additional, Gil-Jimenez, Alberto, additional, de Feijter, Jeantine M., additional, Bekers, Elise, additional, van der Laan, Elsbeth, additional, Lopez-Yurda, Marta, additional, Hooijberg, Erik, additional, Broeks, Annegien, additional, Peters, Dennis, additional, Seignette, Iris M., additional, Pos, Floris J., additional, Horenblas, Simon, additional, van Rhijn, Bas W.G., additional, Jordanova, Ekaterina S., additional, Brouwer, Oscar R., additional, Schaake, Eva, additional, and van der Heijden, Michiel S., additional

Published
2023
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45. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

Author

Powles, Thomas, Kockx, Mark, Rodriguez-Vida, Alejo, Duran, Ignacio, Crabb, Simon J., Van Der Heijden, Michiel S., and Szabados, Bernadett

Subjects
Gene expression -- Research, Bone morphogenetic proteins -- Research, Biological sciences, Health
Abstract

Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers.sup.1,2. Biomarkers may facilitate identification of these responding tumors.sup.3. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer.sup.4-7. Sequential tissue sampling from these studies allowed for detailed on-treatment biomarker analysis. Here, we present a single-arm phase 2 study, investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer (ClinicalTrials.gov identifier: (https://clinicaltrials.gov/ct2/show/NCT02662309?term=NCT02662309&rank=1)). Pathological complete response was the primary endpoint. Secondary endpoints focused on safety, relapse-free survival and biomarker analysis. The pathological complete response rate was 31% (95% confidence interval: 21-41%), achieving the primary efficacy endpoint. Baseline biomarkers showed that the presence of preexisting activated T cells was more prominent than expected and correlated with outcome. Other established biomarkers, such as tumor mutational burden, did not predict outcome, differentiating this from the metastatic setting. Dynamic changes to gene expression signatures and protein biomarkers occurred with therapy, whereas changes in DNA alterations with treatment were uncommon. Responding tumors showed predominant expression of genes related to tissue repair after treatment, making tumor biomarker interpretation challenging in this group. Stromal factors such as transforming growth factor-[beta] and fibroblast activation protein were linked to resistance, as was high expression of cell cycle gene signatures after treatment. A single-arm multicenter phase 2 trial demonstrates clinical efficacy of neoadjuvant PD-L1 blockade in patients with resectable muscle-invasive bladder cancer ineligible for cisplatin and examines biomarkers associated with patient outcome., Author(s): Thomas Powles [sup.1] , Mark Kockx [sup.2] , Alejo Rodriguez-Vida [sup.3] , Ignacio Duran [sup.4] , Simon J. Crabb [sup.5] , Michiel S. Van Der Heijden [sup.6] , Bernadett [...]

Published
2019
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49. Corrigendum to “Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer” [Eur Urol 2023;83:313–17]

Author

Gil-Jimenez, Alberto, primary, van Dorp, Jeroen, additional, Contreras-Sanz, Alberto, additional, van der Vos, Kristan, additional, Vis, Daniel J., additional, Braaf, Linde, additional, Broeks, Annegien, additional, Kerkhoven, Ron, additional, van Kessel, Kim E.M., additional, Ribal, María José, additional, Alcaraz, Antonio, additional, Wessels, Lodewyk F.A., additional, Seiler, Roland, additional, Wright, Jonathan L., additional, Mengual, Lourdes, additional, Boormans, Joost, additional, van Rhijn, Bas W.G., additional, Black, Peter C., additional, and van der Heijden, Michiel S., additional

Published
2023
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50. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Author

Wong, Suet-Lai Shirley, Tan, Thean Hsiang, Hovey, Elizabeth Jane, Clay, Timothy Dudley, Ng, Siobhan Su Wan, Rutten, Annemie, Machiels, Jean-Pascal, Dumez, Herlinde, Cheng, Susanna Yee-Shan, Chi, Kim Nguyen, Ferrario, Cristiano, Sengeloev, Lisa, Jensen, Niels Viggo, Thibault, Constance, Laguerre, Brigitte, Laestadius, Fredrik, Joly, Florence, Flechon, Aude, Culine, Stéphane, Becht, Catherine, Niegisch, Günter, Stöckle, Michael, Grimm, Marc-Oliver, Gakis, Georgios, Schultze-Seemann, Wolfgang, Kalofonos, Haralambos, Mavroudis, Dimitrios, Papandreou, Christos, Karavasilis, Vasilis, Bamias, Aristotelis, Révész, Janos, Geczi, Lajos, Rosenbaum, Eli, Leibowitz-Amit, Raya, Kejzman, Daniel, Peer, Avivit, Sarid, David, Scagliotti, Giorgio Vittorio, Sternberg, Cora N, Tortora, Giampaolo, Bracarda, Sergio, Necchi, Andrea, Massari, Francesco, Osawa, Takahiro, Miyajima, Naoto, Shinohara, Nobuo, Fukuta, Fumimasa, Ohyama, Chikara, Obara, Wataru, Yamashita, Shinichi, Tomita, Yoshihiko, Kawai, Koji, Fukasawa, Satoshi, Matsubara, Nobuaki, Oyama, Masafumi, Yonese, Junji, Nagata, Masayoshi, Uemura, Motohide, Nishimura, Kazuo, Kawakita, Mutsushi, Tsunemori, Hiroyuki, Hashine, Katsuyoshi, Inokuchi, Junichi, Yokomizo, Akira, Nagamori, Satoshi, Lee, Jae-Lyun, Lee, Hyo Jin, Park, Se Hoon, Rha, Sun Young, Kim, Yu Jung, Lee, Yun-Gyoo, Cortés, Leticia Vazquez, Flores, Claudia Lorena Urzua, Blaisse, Reinoud J B, van der Heijden, Michiel S, de Wit, Ronald, Erdkamp, Fransiscus L G, Aarts, Maureen J B, Wojcik-Tomaszewska, Joanna, Tomczak, Piotr, Sikora-Kupis, Bozena, Schenker, Michael, Herzal, Alina Amalia, Udrea, Anghel Adrian, Karlov, Petr, Safina, Sufia Z, Alekseev, Boris, Semenov, Andrey, Fomkin, Roman, Pulido, Enrique Grande, Del Muro, F Xavier García, Mignorance, Juan Ignacio Delgado, Gauna, Daniel Castellano, Rodríguez-Vida, Alejo, Su, Yu-Li, Ou, Yen-Chuan, Lin, Chien-Liang, Su, Wen-Pin, Lin, Chia-Chi, Yeh, Su-Peng, Çiçin, Irfan, Harputluoglu, Hakan, Erman, Mustafa, Coskun, Hasan Senol, Urun, Yuksel, Golovko, Yurii, Bondarenko, Igor, Sinielnikov, Ivan, Powles, Thomas, Crabb, Simon, Syndikus, Isabel, Huddart, Robert, Sundar, Santhanam, Chowdhury, Simon, Sarwar, Naveed, Drakaki, Alexandra, Flaig, Thomas, Pan, Chong Xian, Petrylak, Daniel, Schwarz, James, Percent, Ivor, Cultrera, Jennifer, Hainsworth, John, Herms, Benjamin, Lawler, William, Lowe, Thomas, Tagawa, Scott, Aragon-Ching, Jeanny, Vaishampayan, Ulka, Petrylak, Daniel P, Chi, Kim N, Nishiyama, Hiroyuki, Castellano, Daniel, Hussain, Syed, Fléchon, Aude, Yu, Evan Y, Géczi, Lajos, Hegemann, Miriam, Percent, Ivor J, Tucci, Marcello, Safina, Sufia, del Muro, Xavier Garcia, Rodriguez-Vida, Alejo, Cicin, Irfan, Widau, Ryan C, Liepa, Astra M, Walgren, Richard A, Hamid, Oday, Zimmermann, Annamaria H, and Bell-McGuinn, Katherine M

Published
2017
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