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1. Sparse-Input Neural Network using Group Concave Regularization

Author

Luo, Bin and Halabi, Susan

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

Simultaneous feature selection and non-linear function estimation are challenging, especially in high-dimensional settings where the number of variables exceeds the available sample size in modeling. In this article, we investigate the problem of feature selection in neural networks. Although the group LASSO has been utilized to select variables for learning with neural networks, it tends to select unimportant variables into the model to compensate for its over-shrinkage. To overcome this limitation, we propose a framework of sparse-input neural networks using group concave regularization for feature selection in both low-dimensional and high-dimensional settings. The main idea is to apply a proper concave penalty to the $l_2$ norm of weights from all outgoing connections of each input node, and thus obtain a neural net that only uses a small subset of the original variables. In addition, we develop an effective algorithm based on backward path-wise optimization to yield stable solution paths, in order to tackle the challenge of complex optimization landscapes. Our extensive simulation studies and real data examples demonstrate satisfactory finite sample performances of the proposed estimator, in feature selection and prediction for modeling continuous, binary, and time-to-event outcomes.

Published
2023

2. Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial

Author

Lopes, Renato D, Higano, Celestia S, Slovin, Susan F, Nelson, Adam J, Bigelow, Robert, Sørensen, Per S, Melloni, Chiara, Goodman, Shaun G, Evans, Christopher P, Nilsson, Jan, Bhatt, Deepak L, Clarke, Noel W, Olesen, Tine K, Doyle-Olsen, Belinda T, Kristensen, Henriette, Arney, Lauren, Roe, Matthew T, Alexander, John H, Mol-Arts, Mirjam, Mansor-Lefebvre, Samreen, Zubovskiy, Konstantin, Blemings, Allan, Dugi, Klaus, Bloomfield, Gerald, Kontos, Chris, DeVore, Adam, Jordan, Dedrick, Kolls, Bradley, Matthews, Robin, Mehta, Rajendra, Povsic, Thomas J, Morse, Michael, Mahaffey, Kenneth W, Halabi, Susan, Leong, Darryl, Klotz, Laurence, Fleshner, Neil, Jansz, Godfrey, Giddens, Jonathan, Egerdie, Russell, Chin, Joseph, Zadra, Joseph, Casey, Richard, Simard, Jean, Niazi, Tamim, Martin, André-Guy, Babjuk, Marek, Hajek, Jaroslav, Klecka, Jiri, Kubes, Jiri, Schraml, Jan, Jakesova, Jitka, Vanasek, Jaroslav, Melichar, Bohuslav, Seikkula, Heikki, Abdiche, Manouar Samir, Colombel, Marc, Debourdeau, Philippe, Robert, Gregoire, Villers, Arnauld, Ploussard, Guillaume, Pradere, Benjamin, Bruyere, Franck, Descotes, Jean-Luc, Ouzaid, Idir, Winter, Alexander, Hanitzsch, Herbert, Sperling, Herbert, Eckert, Ralf, Hammerer, Peter, Stagge, Elke, Seseke, Florian, Szymula, Silvio, Bamias, Aristotelis, Thanos, Anastasios, Hatzimouratidis, Konstantinos, Mamoulakis, Charalambos, Kalofonos, Haralabos, Oszukowska, Elzbieta, Madziarska, Katarzyna, Fijuth, Jacek, Obarzanowski, Mateusz, Alekseev, Boris, Atduev, Vagif, Pushkar, Dmitri, Veliev, Evgeniy, Zyryanov, Alexander, Petrov, Sergey, Kopyltsov, Evgeny, Kozlov, Vadim, Macko, Ladislav, Dubravicky, Jozef, Polak, Richard, Mir, Obaidullah, Vargovcak, Marek, Mincik, Ivan, Kliment, Jan, Goncalves, Frederico, Mikulas, Juraj, and Sokol, Roman

Subjects
Cancer, Clinical Trials and Supportive Activities, Patient Safety, Aging, Prostate Cancer, Urologic Diseases, Cardiovascular, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Aged, Humans, Leuprolide, Male, Oligopeptides, Prospective Studies, Prostatic Neoplasms, agonists, atherosclerosis, cardiotoxicity, drug therapy, gonadotropin-releasing hormone, prostatic neoplasms, PRONOUNCE Study Investigators, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundThe relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.MethodsIn this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.ResultsBecause of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).ConclusionsPRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.

Published
2021

3. Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium

Author

Choueiri, Toni K., Labaki, Chris, Bakouny, Ziad, Hsu, Chih-Yuan, Schmidt, Andrew L., de Lima Lopes, Gilberto, Jr., Hwang, Clara, Singh, Sunny R.K., Jani, Chinmay, Weissmann, Lisa B., Griffiths, Elizabeth A., Halabi, Susan, Wu, Ulysses, Berg, Stephanie, O'Connor, Timothy E., Wise-Draper, Trisha M., Panagiotou, Orestis A., Klein, Elizabeth J., Joshi, Monika, Yared, Fares, Dutra, Miriam Santos, Gatson, Na Tosha N., Blau, Sibel, Singh, Harpreet, Nanchal, Rahul, McKay, Rana R., Nonato, Taylor K., Quinn, Ryann, Rubinstein, Samuel M., Puc, Matthew, Mavromatis, Blanche H., Vikas, Praveen, Faller, Bryan, Zaren, Howard A., Del Prete, Salvatore, Russell, Karen, Reuben, Daniel Y., Accordino, Melissa K., Friese, Christopher R., Mishra, Sanjay, Rivera, Donna R., Shyr, Yu, Farmakiotis, Dimitrios, and Warner, Jeremy L.

Published
2023
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4. Common variation in a long non-coding RNA gene modulates variation of circulating TGF-β2 levels in metastatic colorectal cancer patients (Alliance)

Author

Quintanilha, Julia C.F., primary, Sibley, Alexander B., additional, Liu, Yingmiao, additional, Niedzwiecki, Donna, additional, Halabi, Susan, additional, Rogers, Layne, additional, O’Neil, Bert, additional, Kindler, Hedy, additional, Kelly, William, additional, Venook, Alan, additional, McLeod, Howard L., additional, Ratain, Mark J., additional, Nixon, Andrew B., additional, Innocenti, Federico, additional, and Owzar, Kouros, additional

Published
2024
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5. Adaptation of the socioecological model to address disparities in engagement of Black men in prostate cancer genetic testing.

Author

Leader, Amy E., Rebbeck, Timothy R., Oh, William K., Patel, Alpa V., Winer, Eric P., Bailey, LeeAnn O., Gomella, Leonard G., Lumpkins, Crystal Y., Garraway, Isla P., Aiello, Lisa B., Baskin, Monica L., Cheng, Heather H., Cooney, Kathleen A., Ganzak, Amanda, George, Daniel J., Halabi, Susan, Hathaway, Feighanne, Healy, Claire, Kim, Joseph W., and Leapman, Michael S.

Subjects
BLACK men, MEDICAL personnel, PROSTATE cancer patients, HEALTH equity, COMMUNITY-based programs
Abstract

Background: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. Methods: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. Results: All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65–4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). Conclusion: The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Radiographic Progression-Free Survival and Clinical Progression-Free Survival as Potential Surrogates for Overall Survival in Men With Metastatic Hormone-Sensitive Prostate Cancer

Author

Halabi, Susan, Roy, Akash, Rydzewska, Larysa, Guo, Siyuan, Godolphin, Peter, Hussain, Maha, Tangen, Catherine, Thompson, Ian, Xie, Wanling, Carducci, Michael A., Smith, Matthew R., Morris, Michael J., Gravis, Gwenaelle, Dearnaley, David P., Verhagen, Paul, Goto, Takayuki, James, Nick, Buyse, Marc E., Tierney, Jayne F., Sweeney, Christopher, Halabi, Susan, Roy, Akash, Rydzewska, Larysa, Guo, Siyuan, Godolphin, Peter, Hussain, Maha, Tangen, Catherine, Thompson, Ian, Xie, Wanling, Carducci, Michael A., Smith, Matthew R., Morris, Michael J., Gravis, Gwenaelle, Dearnaley, David P., Verhagen, Paul, Goto, Takayuki, James, Nick, Buyse, Marc E., Tierney, Jayne F., and Sweeney, Christopher

Abstract

PURPOSEDespite major increases in the longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC), most men still die of prostate cancer. Phase III trials assessing new therapies in mHSPC with overall survival (OS) as the primary end point will take approximately a decade to complete. We investigated whether radiographic progression-free survival (rPFS) and clinical PFS (cPFS) are valid surrogates for OS in men with mHSPC and could potentially be used to expedite future phase III clinical trials.METHODSWe obtained individual patient data (IPD) from 9 eligible randomized trials comparing treatment regimens (different androgen deprivation therapy [ADT] strategies or ADT plus docetaxel in the control or research arms) in mHSPC. rPFS was defined as the time from random assignment to radiographic progression or death from any cause whichever occurred first; cPFS was defined as the time from random assignment to the date of radiographic progression, symptoms, initiation of new treatment, or death, whichever occurred first. We implemented a two-stage meta-analytic validation model where conditions of patient-level and trial-level surrogacy had to be met. We then computed the surrogate threshold effect (STE).RESULTSIPD from 6,390 patients randomly assigned from 1994 to 2012 from 13 units were pooled for a stratified analysis. The median OS, rPFS, and cPFS were 4.3 (95% CI, 4.2 to 4.5), 2.4 (95% CI, 2.3 to 2.5), and 2.3 years (95% CI, 2.2 to 2.4), respectively. The STEs were 0.80 and 0.81 for rPFS and cPFS end points, respectively.CONCLUSIONBoth rPFS and cPFS appear to be promising surrogate end points for OS. The STE of 0.80 or higher makes it viable for either rPFS or cPFS to be used as the primary end point that is surrogate for OS in phase III mHSPC trials with testosterone suppression alone as the backbone therapy and would expedite trial conduct.

Published
2024

7. A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer

Author

Zhao, Shuang G., Sperger, Jamie M., Schehr, Jennifer L., McKay, Rana R., Emamekhoo, Hamid, Singh, Anupama, Schultz, Zachery D., Bade, Rory M., Stahlfeld, Charlotte N., Gilsdorf, Cole S., Hernandez, Camila I., Wolfe, Serena K., Mayberry, Richel D., Krause, Hannah M., Bootsma, Matt, Helzer, Kyle T., Rydzewski, Nicholas, Bakhtiar, Hamza, Shi, Yue, Blitzer, Grace, Kyriakopoulos, Christos E., Kosoff, David, Wei, Xiao X., Floberg, John, Sethakorn, Nan, Sharifi, Marina, Harari, Paul M., Huang, Wei, Beltran, Himisha, Choueiri, Toni K., Scher, Howard I., Rathkopf, Dana E., Halabi, Susan, Armstrong, Andrew J., Beebe, David J., Yu, Menggang, Sundling, Kaitlin E., Taplin, Mary-Ellen, and Lang, Joshua M.

Subjects
Prostate cancer -- Development and progression -- Prognosis, Tumor markers -- Genetic aspects -- Health aspects, Health care industry
Abstract

BACKGROUND. Neuroendocrine prostate cancer (NEPC) is an aggressive subtype, the presence of which changes the prognosis and management of metastatic prostate cancer. METHODS. We performed analytical validation of a Circulating Tumor Cell (CTC) multiplex RNA qPCR assay to identify the limit of quantification (LOQ) in cell lines, synthetic cDNA, and patient samples. We next profiled 116 longitudinal samples from a prospectively collected institutional cohort of 17 patients with metastatic prostate cancer (7 NEPC, 10 adenocarcinoma) as well as 265 samples from 139 patients enrolled in 3 adenocarcinoma phase II trials of androgen receptor signaling inhibitors (ARSIs). We assessed a NEPC liquid biomarker via the presence of neuroendocrine markers and the absence of androgen receptor (AR) target genes. RESULTS. Using the analytical validation LOQ, liquid biomarker NEPC detection in the longitudinal cohort had a per- sample sensitivity of 51.35% and a specificity of 91.14%. However, when we incorporated the serial information from multiple liquid biopsies per patient, a unique aspect of this study, the per-patient predictions were 100% accurate, with a receiver- operatingcurve (ROC) AUC of 1. In the adenocarcinoma ARSI trials, the presence of neuroendocrine markers, even while AR target gene expression was retained, was a strong negative prognostic factor. CONCLUSION. Our analytically validated CTC biomarker can detect NEPC with high diagnostic accuracy when leveraging serial samples that are only feasible using liquid biopsies. Patients with expression of NE genes while retaining AR- target gene expression may indicate the transition to neuroendocrine differentiation, with clinical characteristics consistent with this phenotype. FUNDING. NIH (DP2 OD030734, 1UH2CA260389, R01CA247479, and P30 CA014520), Department of Defense (PC190039 and PC200334), and Prostate Cancer Foundation (Movember Foundation--PCF Challenge Award)., Introduction The majority of prostate cancers are histologically classified as adenocarcinomas. Prostate adenocarcinoma is driven by androgens, expresses prostate-specific antigen (PSA) and other androgen receptor (AR) target genes, and responds [...]

Published
2022
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8. Molecular features of prostate cancer after neoadjuvant therapy in the phase 3 CALGB 90203 trial

Author

Sumiyoshi, Takayuki, primary, Wang, Xiaofei, additional, Warner, Evan W, additional, Sboner, Andrea, additional, Annala, Matti, additional, Sigouros, Michael, additional, Beja, Kevin, additional, Mizuno, Kei, additional, Ku, Shengyu, additional, Fazli, Ladan, additional, Eastham, James, additional, Taplin, Mary-Ellen, additional, Simko, Jeffrey, additional, Halabi, Susan, additional, Morris, Michael J, additional, Gleave, Martin E, additional, Wyatt, Alexander W, additional, and Beltran, Himisha, additional

Published
2023
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9. Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

Author

Gillessen, Silke, Bossi, Alberto, Davis, Ian D., de Bono, Johann, Fizazi, Karim, James, Nicholas D., Mottet, Nicolas, Shore, Neal, Small, Eric, Smith, Matthew, Sweeney, Christopher J., Tombal, Bertrand, Antonarakis, Emmanuel S., Aparicio, Ana M., Armstrong, Andrew J., Attard, Gerhardt, Beer, Tomasz M., Beltran, Himisha, Bjartell, Anders, Blanchard, Pierre, Briganti, Alberto, Bristow, Rob G., Bulbul, Muhammad, Caffo, Orazio, Castellano, Daniel, Castro, Elena, Cheng, Heather H., Chi, Kim N., Chowdhury, Simon, Clarke, Caroline S., Clarke, Noel, Daugaard, Gedske, De Santis, Maria, Duran, Ignacio, Eeles, Ross, Efstathiou, Eleni, Efstathiou, Jason, Ekeke, Onyeanunam Ngozi, Evans, Christopher P., Fanti, Stefano, Feng, Felix Y., Fonteyne, Valerie, Fossati, Nicola, Frydenberg, Mark, George, Dan, Gleave, Martin, Gravis, Gwenaelle, Halabi, Susan, Heinrich, Daniel, Herrmann, Ken, Higano, Celestia, Hofman, Michael S., Horvath, Lisa G., Hussain, Maha, Jereczek-Fossa, Barbara A., Jones, Rob, Kanesvaran, Ravindran, Kellokumpu-Lehtinen, Pirkko-Liisa, Khauli, Raja B., Klotz, Laurence, Kramer, Gero, Leibowitz, Raja, Logothetis, Christopher, Mahal, Brandon, Maluf, Fernando, Mateo, Joaquin, Matheson, David, Mehra, Niven, Merseburger, Axel, Morgans, Alicia K., Morris, Michael J., Mrabti, Hind, Mukherji, Deborah, Murphy, Declan G., Murthy, Vedang, Nguyen, Paul L., Oh, William K., Ost, Piet, O'Sullivan, Joe M., Padhani, Anwar R., Pezaro, Carmel J., Poon, Darren M.C., Pritchard, Colin C., Rabah, Danny M., Rathkopf, Dana, Reiter, Robert E., Rubin, Mark A., Ryan, Charles J., Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I., Sharifi, Nima, Skoneczna, Iwona, Soule, Howard, Spratt, Daniel E., Srinivas, Sandy, Sternberg, Cora N., Steuber, Thomas, Suzuki, Hiroyoshi, Sydes, Matthew R., Taplin, Mary-Ellen, Tilki, Derya, Türkeri, Levent, Turco, Fabio, Uemura, Hiroji, Uemura, Hirotsugu, Ürün, Yüksel, Vale, Claire L., van Oort, Inge, Vapiwala, Neha, Walz, Jochen, Yamoah, Kosj, Ye, Dingwei, Yu, Evan Y., Zapatero, Almudena, Zilli, Thomas, Omlin, Aurelius, and O’Sullivan, Joe M.

Subjects
Cancer Research, Systemic therapy, Next-generation imaging, Metastatic castration-resistant prostate cancer (mCRPC) and oligometastatic and oligoprogressive prostate cancer, Metastatic hormone-sensitive prostate cancer (mHSPC), Medizin, PSMA PET-imaging, All institutes and research themes of the Radboud University Medical Center, Oncology, Androgen receptor pathway inhibitors (ARPI), SDG 3 - Good Health and Well-being, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Non metastatic castration-resistant prostate cancer (nmCRPC), Chemotherapy, Hormonal treatment
Abstract

BackgroundInnovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence.ObjectiveTo present the voting results of the APCCC 2022.Design, setting, and participantsThe experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions.Outcome measurements and statistical analysisThe panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions.Results and limitationsThe voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer.ConclusionsThese voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials.

Published
2023

10. Abstract CT226: Crizotinib (C) in patients (pts) with solid tumors with MET amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Author

Mileham, Kathryn F., primary, Rothe, Michael, additional, Mangat, Pam K., additional, Garrett-Mayer, Elizabeth, additional, Duvivier, Herbert L., additional, Calfa, Carmen J., additional, Dul, Carrie L., additional, Marr, Alissa S., additional, Ahn, Eugene R., additional, Behl, Deepti, additional, Hall, Michael J., additional, Mehmi, Inderjit, additional, Gaba, Anu, additional, Leidner, Rom, additional, Zalupski, Mark M., additional, Grantham, Gina N., additional, Gregory, Abigail, additional, Halabi, Susan, additional, and Schilsky, Richard L., additional

Published
2023
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11. Abstract CT231: Temsirolimus (T) in patients (pts) with solid tumors with PTEN mutation (mut): results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Author

Wentzel, Kristopher, primary, Rothe, Michael, additional, Mangat, Pam K., additional, Garrett-Mayer, Elizabeth, additional, Ding, Li, additional, Pisick, Evan, additional, Krishnan, Mridula, additional, Behl, Deepti, additional, Alese, Olatunji B., additional, Calfa, Carmen J., additional, Cooper, Kathrine A., additional, Duvivier, Herbert L., additional, Induru, Raghava Reddy, additional, Ruzich, Janet C., additional, Zhao, Song, additional, Grantham, Gina N., additional, Gregory, Abigail, additional, Halabi, Susan, additional, and Schilsky, Richard L., additional

Published
2023
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12. PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer

Author

Gupta, Santosh, primary, Halabi, Susan, additional, Yang, Qian, additional, Roy, Akash, additional, Tubbs, Alisa, additional, Gore, Yamini, additional, George, Daniel J., additional, Nanus, David M., additional, Antonarakis, Emmanuel S., additional, Danila, Daniel C., additional, Szmulewitz, Russell Z., additional, Wenstrup, Richard, additional, and Armstrong, Andrew J., additional

Published
2023
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13. Management of Patients with Advanced Prostate Cancer. Part I:Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Author

Gillessen, Silke, Bossi, Alberto, Davis, Ian D., de Bono, Johann, Fizazi, Karim, James, Nicholas D., Mottet, Nicolas, Shore, Neal, Small, Eric, Smith, Mathew, Sweeney, Christopher, Tombal, Bertrand, Antonarakis, Emmanuel S., Aparicio, Ana M., Armstrong, Andrew J., Attard, Gerhardt, Beer, Tomasz M., Beltran, Himisha, Bjartell, Anders, Blanchard, Pierre, Briganti, Alberto, Bristow, Rob G., Bulbul, Muhammad, Caffo, Orazio, Castellano, Daniel, Castro, Elena, Cheng, Heather H., Chi, Kim N., Chowdhury, Simon, Clarke, Caroline S., Clarke, Noel, Daugaard, Gedske, De Santis, Maria, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Ngozi Ekeke, Onyeanunam, Evans, Christopher P., Fanti, Stefano, Feng, Felix Y., Fonteyne, Valerie, Fossati, Nicola, Frydenberg, Mark, George, Daniel, Gleave, Martin, Gravis, Gwenaelle, Halabi, Susan, Heinrich, Daniel, Herrmann, Ken, Higano, Celestia, Hofman, Michael S., Horvath, Lisa G., Hussain, Maha, Jereczek-Fossa, Barbara Alicja, Jones, Robert, Kanesvaran, Ravindran, Kellokumpu-Lehtinen, Pirkko Liisa, Khauli, Raja B., Klotz, Laurence, Kramer, Gero, Leibowitz, Raya, Logothetis, Christopher J., Mahal, Brandon A., Maluf, Fernando, Mateo, Joaquin, Matheson, David, Mehra, Niven, Merseburger, Axel, Morgans, Alicia K., Morris, Michael J., Mrabti, Hind, Mukherji, Deborah, Murphy, Declan G., Murthy, Vedang, Nguyen, Paul L., Oh, William K., Ost, Piet, O'Sullivan, Joe M., Padhani, Anwar R., Pezaro, Carmel, Poon, Darren M.C., Pritchard, Colin C., Rabah, Danny M., Rathkopf, Dana, Reiter, Robert E., Rubin, Mark A., Ryan, Charles J., Saad, Fred, Pablo Sade, Juan, Sartor, Oliver A., Scher, Howard I., Sharifi, Nima, Skoneczna, Iwona, Soule, Howard, Spratt, Daniel E., Srinivas, Sandy, Sternberg, Cora N., Steuber, Thomas, Suzuki, Hiroyoshi, Sydes, Matthew R., Taplin, Mary Ellen, Tilki, Derya, Türkeri, Levent, Turco, Fabio, Uemura, Hiroji, Uemura, Hirotsugu, Ürün, Yüksel, Vale, Claire L., van Oort, Inge, Vapiwala, Neha, Walz, Jochen, Yamoah, Kosj, Ye, Dingwei, Yu, Evan Y., Zapatero, Almudena, Zilli, Thomas, Omlin, Aurelius, Gillessen, Silke, Bossi, Alberto, Davis, Ian D., de Bono, Johann, Fizazi, Karim, James, Nicholas D., Mottet, Nicolas, Shore, Neal, Small, Eric, Smith, Mathew, Sweeney, Christopher, Tombal, Bertrand, Antonarakis, Emmanuel S., Aparicio, Ana M., Armstrong, Andrew J., Attard, Gerhardt, Beer, Tomasz M., Beltran, Himisha, Bjartell, Anders, Blanchard, Pierre, Briganti, Alberto, Bristow, Rob G., Bulbul, Muhammad, Caffo, Orazio, Castellano, Daniel, Castro, Elena, Cheng, Heather H., Chi, Kim N., Chowdhury, Simon, Clarke, Caroline S., Clarke, Noel, Daugaard, Gedske, De Santis, Maria, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Ngozi Ekeke, Onyeanunam, Evans, Christopher P., Fanti, Stefano, Feng, Felix Y., Fonteyne, Valerie, Fossati, Nicola, Frydenberg, Mark, George, Daniel, Gleave, Martin, Gravis, Gwenaelle, Halabi, Susan, Heinrich, Daniel, Herrmann, Ken, Higano, Celestia, Hofman, Michael S., Horvath, Lisa G., Hussain, Maha, Jereczek-Fossa, Barbara Alicja, Jones, Robert, Kanesvaran, Ravindran, Kellokumpu-Lehtinen, Pirkko Liisa, Khauli, Raja B., Klotz, Laurence, Kramer, Gero, Leibowitz, Raya, Logothetis, Christopher J., Mahal, Brandon A., Maluf, Fernando, Mateo, Joaquin, Matheson, David, Mehra, Niven, Merseburger, Axel, Morgans, Alicia K., Morris, Michael J., Mrabti, Hind, Mukherji, Deborah, Murphy, Declan G., Murthy, Vedang, Nguyen, Paul L., Oh, William K., Ost, Piet, O'Sullivan, Joe M., Padhani, Anwar R., Pezaro, Carmel, Poon, Darren M.C., Pritchard, Colin C., Rabah, Danny M., Rathkopf, Dana, Reiter, Robert E., Rubin, Mark A., Ryan, Charles J., Saad, Fred, Pablo Sade, Juan, Sartor, Oliver A., Scher, Howard I., Sharifi, Nima, Skoneczna, Iwona, Soule, Howard, Spratt, Daniel E., Srinivas, Sandy, Sternberg, Cora N., Steuber, Thomas, Suzuki, Hiroyoshi, Sydes, Matthew R., Taplin, Mary Ellen, Tilki, Derya, Türkeri, Levent, Turco, Fabio, Uemura, Hiroji, Uemura, Hirotsugu, Ürün, Yüksel, Vale, Claire L., van Oort, Inge, Vapiwala, Neha, Walz, Jochen, Yamoah, Kosj, Ye, Dingwei, Yu, Evan Y., Zapatero, Almudena, Zilli, Thomas, and Omlin, Aurelius

Abstract

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical man

Published
2023

14. Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19

Author

Ko, Emily R., Anstrom, Kevin J., Panettieri, Reynold A., Lachiewicz, Anne M., Maillo, Martin, O’Halloran, Jane A., Boucher, Cynthia, Smith, P. Brian, McCarthy, Matthew W., Segura Nunez, Patricia, Mendivil Tuchia de Tai, Sabina, Khan, Akram, Mena Lora, Alfredo J., Salathe, Matthias, Kedar, Eyal, Capo, Gerardo, Rodríguez Gonzalez, Daniel, Patterson, Thomas F., Palma, Christopher, Ariza, Horacio, Patelli Lima, Maria, Blamoun, John, Nannini, Esteban C., Sprinz, Eduardo, Mykietiuk, Analia, Wang, Jennifer P., Parra-Rodriguez, Luis, Der, Tatyana, Willsey, Kate, Benjamin, Daniel K., Wen, Jun, Zakroysky, Pearl, Halabi, Susan, Silverstein, Adam, McNulty, Steven E., O’Brien, Sean M., Al-Khalidi, Hussein R., Butler, Sandra, Atkinson, Jane, Adam, Stacey J., Chang, Soju, Maldonado, Michael A., Proscham, Michael, LaVange, Lisa, Bozzette, Samuel A., and Powderly, William G.

Subjects
Article
Abstract

BackgroundWe investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.MethodsWe conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality.ResultsBetween October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00–1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41– 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo).ConclusionsAddition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality.Trial registrationClinicalTrials.gov(NCT04593940).

Published
2022

15. Predictive biomarkers of overall survival in patients with advanced renal cell carcinoma treated with interferon alpha +/− bevacizumab: Results from CALGB 90206 (Alliance)

Author

Nixon, Andrew B., Halabi, Susan, Liu, Yingmiao, Starr, Mark D., Brady, John C., Shterev, Ivo, Luo, Bin, Hurwitz, Herbert I., Febbo, Phillip G., Rini, Brian I., Beltran, Himisha, Small, Eric J., Morris, Michael J., and George, Daniel J.

Subjects
Article
Abstract

PURPOSE: CALGB 90206 was a phase III trial of 732 mRCC patients comparing bevacizumab plus interferon alpha (BEV+IFN) versus interferon alpha alone (IFN). No difference in overall survival (OS) was observed. Baseline samples were analyzed to identify predictive biomarkers for survival benefit. EXPERIMENTAL DESIGN: A total of 32 biomarkers were assessed in 498 consenting patients randomly assigned into training (n=279) and testing (n=219) sets. The proportional hazards model was used to test for treatment arm and biomarker interactions of OS. The estimated coefficients from the training set were used to compute a risk score for each patient and to classify patients by risk in the testing set. The resulting model was assessed for predictive accuracy using the time-dependent area under the receiver operating characteristic curve (tAUROC). RESULTS: A statistically significant 3-way interaction between IL-6, HGF, and bevacizumab treatment was observed in the training set and confirmed in the testing set (p

Published
2022

17. Abstract 646: Liquid biopsy transcriptomics identify pathways associated with poor outcomes and immune phenotypes in men with mCRPC

Author

Zhang, Jiaren, primary, Zimmermann, Bob, additional, Galletti, Giuseppe, additional, Halabi, Susan, additional, Gjyrezi, Ada, additional, Yang, Qian, additional, Gupta, Santosh, additional, Verma, Akanksha, additional, Sboner, Andrea, additional, Anand, Monika, additional, George, Daniel J., additional, Gregory, Simon G., additional, Mahtani, Prerna, additional, Hong, Seunghee, additional, Pascual, Virginia, additional, Mavragani, Clio P., additional, Antonarakis, Emmanuel S., additional, Nanus, David M., additional, Tagawa, Scott T., additional, Elemento, Olivier, additional, Armstrong, Andrew J., additional, and Giannakakou, Paraskevi, additional

Published
2022
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18. Abstract CT110: Olaparib (O) in patients (pts) with solid tumors with ATM mutation or deletion: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Author

Mileham, Kathryn F., primary, Rothe, Michael, additional, Mangat, Pam K., additional, Garrett-Mayer, Elizabeth, additional, Yang, Eddy S., additional, Alese, Olatunji B., additional, Jain, Angela, additional, Duvivier, Herbert L., additional, Palmbos, Phillip, additional, Ahn, Eugene R., additional, Aragon-Ching, Jeanny B., additional, Beekman, Kathleen W., additional, Behl, Deepti, additional, Meric-Bernstam, Funda, additional, Gutierrez, Rodolfo, additional, Sanford, Amy, additional, Thota, Ramya, additional, Zakem, Michael, additional, Zhao, Song, additional, O'Lone, Raegan, additional, Grantham, Gina N., additional, Halabi, Susan, additional, and Schilsky, Richard L., additional

Published
2022
Full Text
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19. What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Turco, Fabio, Armstrong, Andrew, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Rob G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline S, Clarke, Noel, Davis, Ian D, de Bono, Johann, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celestia, Hofman, Michael S, Hussain, Maha, James, Nicholas, Jones, Rob, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Christopher, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ekeke, Onyeanunam N, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Christopher, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel E, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew R, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Gillessen, Silke, Omlin, Aurelius, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Turco, Fabio, Armstrong, Andrew, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Rob G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline S, Clarke, Noel, Davis, Ian D, de Bono, Johann, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celestia, Hofman, Michael S, Hussain, Maha, James, Nicholas, Jones, Rob, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Christopher, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ekeke, Onyeanunam N, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Christopher, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel E, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew R, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Gillessen, Silke, and Omlin, Aurelius

Abstract

Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic. There was a consensus for full COVID-19 vaccination and booster injection in APC patients. Furthermore, the voting results indicate that the expert's treatment recommendations are influenced by the vaccination status: the COVID-19 pandemic altered management of APC patients for 70% of the panellists before the vaccination was available but only for 25% of panellists for fully vaccinated patients. Most experts (71%) were less likely to use docetaxel and abiraterone in unvaccinated patients with metastatic hormone-sensitive prostate cancer. For fully vaccinated patients with high-risk localised prostate cancer, there was a consensus (77%) to follow the usual treatment schedule, whereas in unvaccinated patients, 55% of the panel members voted for deferring radiation therapy. Finally, there was a strong consensus for the use of telemedicine for monitoring APC patients. PATIENT SUMMARY: In the Advanced Prostate Cancer Consensus Conference 2021, the panellists reached a consensus regarding the recommendation of the COVID-19 vaccine in prostate cancer patients and use of telemedicine for monitoring these patients.

Published
2022

20. Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Gillessen, Silke, Armstrong, Andrew, Attard, Gert, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Robert G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline S, Clarke, Noel, Davis, Ian D, de Bono, Johann S, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Ekeke, Onyeanunam Ngozi, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celesta, Hofman, Michael S, Hussain, Maha, James, Nick, Jones, Robert, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Chris, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Chris, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Rob E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan P, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel E, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew R, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Omlin, Aurelius, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Gillessen, Silke, Armstrong, Andrew, Attard, Gert, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Robert G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline S, Clarke, Noel, Davis, Ian D, de Bono, Johann S, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Ekeke, Onyeanunam Ngozi, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celesta, Hofman, Michael S, Hussain, Maha, James, Nick, Jones, Robert, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Chris, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Chris, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Rob E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan P, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel E, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew R, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, and Omlin, Aurelius

Abstract

Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. To present the voting results from APCCC 2021. The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identi

Published
2022

21. Corrigendum to 'What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021' [Eur Urol 2022].

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Turco, Fabio, Armstrong, Andrew, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Rob G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline, Clarke, Noel, Davis, Ian D, de Bono, Johann, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celestia, Hofman, Michael S, Hussain, Maha, James, Nicholas, Jones, Rob, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Christopher, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ekeke, Onyeanunam Ngozi, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Christopher, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Gillessen, Silke, Omlin, Aurelius, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Turco, Fabio, Armstrong, Andrew, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Rob G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline, Clarke, Noel, Davis, Ian D, de Bono, Johann, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celestia, Hofman, Michael S, Hussain, Maha, James, Nicholas, Jones, Rob, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Christopher, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ekeke, Onyeanunam Ngozi, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Christopher, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Gillessen, Silke, and Omlin, Aurelius

Published
2022

22. Lack of consensus identifies important areas for future clinical research: Advanced Prostate Cancer Consensus Conference (APCCC) 2019 findings.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Vogl, Ursula M, Beer, Tomasz M, Davis, Ian D, Shore, Neal D, Sweeney, Christopher J, Ost, Piet, Attard, Gerhardt, Bossi, Alberto, de Bono, Johann, Drake, Charles G, Efstathiou, Eleni, Fanti, Stefano, Fizazi, Karim, Halabi, Susan, James, Nicolas, Mottet, Nicolas, Padhani, Anwar R, Roach, Mack, Rubin, Mark, Sartor, Oliver, Small, Eric, Smith, Matthew R, Soule, Howard, Sydes, Matthew R, Tombal, Bertrand, Omlin, Aurelius, Gillessen, Silke, APCCC 2019 expert panel, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Vogl, Ursula M, Beer, Tomasz M, Davis, Ian D, Shore, Neal D, Sweeney, Christopher J, Ost, Piet, Attard, Gerhardt, Bossi, Alberto, de Bono, Johann, Drake, Charles G, Efstathiou, Eleni, Fanti, Stefano, Fizazi, Karim, Halabi, Susan, James, Nicolas, Mottet, Nicolas, Padhani, Anwar R, Roach, Mack, Rubin, Mark, Sartor, Oliver, Small, Eric, Smith, Matthew R, Soule, Howard, Sydes, Matthew R, Tombal, Bertrand, Omlin, Aurelius, Gillessen, Silke, and APCCC 2019 expert panel

Abstract

Innovations in treatments, imaging and molecular characterisation have improved outcomes for people with advanced prostate cancer; however, many aspects of clinical management are devoid of high-level evidence. At the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, many of these topics were addressed, and consensus was not always reached. The results from clinical trials will most reliably plus the gaps. An invited panel of 57 experts voted on 123 multiple-choice questions on clinical management at APCCC 2019. No consensus was reached on 88 (71.5%) questions defined as <75% of panellists voting for the same answer option. We reviewed clinicaltrials.gov to identify relevant ongoing phase III trials in these areas of non-consensus. A number of ongoing phase III trials were identified that are relevant to these non-consensus issues. However, many non-consensus issues appear not to be addressed by current clinical trials. Of note, no phase III but only phase II trials were identified, investigating side effects of hormonal treatments and their management. Lack of consensus almost invariable indicates gaps in existing evidence. The high percentage of questions lacking consensus at APCCC 2019 highlights the complexity of advanced prostate cancer care and the need for robust, clinically relevant trials that can fill current gaps with high-level evidence. Our review of these areas of non-consensus and ongoing trials provides a useful summary, indicating areas in which future consensus may soon be reached. This review may facilitate academic investigators to identify and prioritise topics for future research.

Published
2022

23. Management of patients with advanced prostate cancer. Part I: intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: report of the Advanced Prostate Cancer Consensus Conference 2022

Author

Tilki, Derya, Gillessen, Silke; Bossi, Alberto; Davis, Ian D.; de Bono, Johann; Fizazi, Karim; James, Nicholas D.; Mottet, Nicolas; Shore, Neal; Small, Eric; Smith, Mathew; Sweeney, Christopher; Tombal, Bertrand; Antonarakis, Emmanuel S.; Aparicio, Ana M.; Armstrong, Andrew J.; Attard, Gerhardt; Beer, Tomasz M.; Beltran, Himisha; Bjartell, Anders; Blanchard, Pierre; Briganti, Alberto; Bristow, Rob G.; Bulbul, Muhammad; Caffo, Orazio; Castellano, Daniel; Castro, Elena; Cheng, Heather H.; Chi, Kim N.; Chowdhury, Simon; Clarke, Caroline S.; Clarke, Noel; Daugaard, Gedske; De Santis, Maria; Duran, Ignacio; Eeles, Ros; Efstathiou, Eleni; Efstathiou, Jason; Ngozi Ekeke, Onyeanunam; Evans, Christopher P.; Fanti, Stefano; Feng, Felix Y.; Fonteyne, Valerie; Fossati, Nicola; Frydenberg, Mark; George, Daniel; Gleave, Martin; Gravis, Gwenaelle; Halabi, Susan; Heinrich, Daniel; Herrmann, Ken; Higano, Celestia; Hofman, Michael S.; Horvath, Lisa G.; Hussain, Maha; Jereczek-Fossa, Barbara Alicja; Jones, Robert; Kanesvaran, Ravindran; Kellokumpu-Lehtinen, Pirkko-Liisa; Khauli, Raja B.; Klotz, Laurence; Kramer, Gero; Leibowitz, Raya; Logothetis, Christopher J.; Mahal, Brandon A.; Maluf, Fernando; Mateo, Joaquin; Matheson, David; Mehra, Niven; Merseburger, Axel; Morgans, Alicia K.; Morris, Michael J.; Mrabti, Hind; Mukherji, Deborah; Murphy, Declan G.; Murthy, Vedang; Nguyen, Paul L.; Oh, William K.; Ost, Piet; O'Sullivan, Joe; Padhani, Anwar R.; Pezaro, Carmel; Poon, Darren M.C.; Pritchard, Colin C.; Rabah, Danny M.; Rathkopf, Dana; Reiter, Robert E.; Rubin, Mark. A.; Ryan, Charles J.; Saad, Fred; Pablo Sade, Juan; Sartor, Oliver A.; Scher, Howard I.; Sharifi, Nima; Skoneczna, Iwona; Soule, Howard; Spratt, Daniel E.; Srinivas, Sandy; Sternberg, Cora N.; Steuber, Thomas; Suzuki, Hiroyoshi; Sydes, Matthew R.; Taplin, Mary-Ellen; Türkeri, Levent; Turco, Fabio; Uemura, Hiroji; Uemura, Hirotsugu; Ürün, Yüksel; Vale, Claire L.; van Oort, Inge; Vapiwala, Neha; Walz, Jochen; Yamoah, Kosj; Ye, Dingwei; Yu, School of Medicine, Tilki, Derya, Gillessen, Silke; Bossi, Alberto; Davis, Ian D.; de Bono, Johann; Fizazi, Karim; James, Nicholas D.; Mottet, Nicolas; Shore, Neal; Small, Eric; Smith, Mathew; Sweeney, Christopher; Tombal, Bertrand; Antonarakis, Emmanuel S.; Aparicio, Ana M.; Armstrong, Andrew J.; Attard, Gerhardt; Beer, Tomasz M.; Beltran, Himisha; Bjartell, Anders; Blanchard, Pierre; Briganti, Alberto; Bristow, Rob G.; Bulbul, Muhammad; Caffo, Orazio; Castellano, Daniel; Castro, Elena; Cheng, Heather H.; Chi, Kim N.; Chowdhury, Simon; Clarke, Caroline S.; Clarke, Noel; Daugaard, Gedske; De Santis, Maria; Duran, Ignacio; Eeles, Ros; Efstathiou, Eleni; Efstathiou, Jason; Ngozi Ekeke, Onyeanunam; Evans, Christopher P.; Fanti, Stefano; Feng, Felix Y.; Fonteyne, Valerie; Fossati, Nicola; Frydenberg, Mark; George, Daniel; Gleave, Martin; Gravis, Gwenaelle; Halabi, Susan; Heinrich, Daniel; Herrmann, Ken; Higano, Celestia; Hofman, Michael S.; Horvath, Lisa G.; Hussain, Maha; Jereczek-Fossa, Barbara Alicja; Jones, Robert; Kanesvaran, Ravindran; Kellokumpu-Lehtinen, Pirkko-Liisa; Khauli, Raja B.; Klotz, Laurence; Kramer, Gero; Leibowitz, Raya; Logothetis, Christopher J.; Mahal, Brandon A.; Maluf, Fernando; Mateo, Joaquin; Matheson, David; Mehra, Niven; Merseburger, Axel; Morgans, Alicia K.; Morris, Michael J.; Mrabti, Hind; Mukherji, Deborah; Murphy, Declan G.; Murthy, Vedang; Nguyen, Paul L.; Oh, William K.; Ost, Piet; O'Sullivan, Joe; Padhani, Anwar R.; Pezaro, Carmel; Poon, Darren M.C.; Pritchard, Colin C.; Rabah, Danny M.; Rathkopf, Dana; Reiter, Robert E.; Rubin, Mark. A.; Ryan, Charles J.; Saad, Fred; Pablo Sade, Juan; Sartor, Oliver A.; Scher, Howard I.; Sharifi, Nima; Skoneczna, Iwona; Soule, Howard; Spratt, Daniel E.; Srinivas, Sandy; Sternberg, Cora N.; Steuber, Thomas; Suzuki, Hiroyoshi; Sydes, Matthew R.; Taplin, Mary-Ellen; Türkeri, Levent; Turco, Fabio; Uemura, Hiroji; Uemura, Hirotsugu; Ürün, Yüksel; Vale, Claire L.; van Oort, Inge; Vapiwala, Neha; Walz, Jochen; Yamoah, Kosj; Ye, Dingwei; Yu, and School of Medicine

Abstract

Background: innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: to present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: consensus was defined as ?75% agreement, with strong consensus defined as ?90% agreement. Results and limitations: the voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: these voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical manage, We gratefully acknowledge the following organisations for providing financial support for the APCCC 2022: The City of Lugano and Movember Foundation. Ros Eeles is supported by a National Institute of Health Research grant to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. We also acknowledge sponsorship from several for-profit organisations for APCCC 2022, including Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer Health Care, Debio-pharm, MSD, Janssen Oncology, Myovant Sciences, Orion Pharma, Pfizer Oncology, Roche, Telix Innovations SA, Ferring Pharmaceuticals, Lantheus, and Tolmar. These for-profit organisations supported the conference financially but had no input on the scientific content or the final publication.

Published
2022

24. Corrigendum to 'What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021' [Eur Urol 2022]

Author

Turco, Fabio, Armstrong, Andrew, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bjartell, Anders, Bossi, Alberto, Briganti, Alberto, Bristow, Rob G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline, Clarke, Noel, Davis, Ian D, de Bono, Johann, Duran, Ignacio, Eeles, Ros, Efstathiou, Eleni, Efstathiou, Jason, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celestia, Hofman, Michael S, Hussain, Maha, James, Nicholas, Jones, Rob, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Christopher, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicolas, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ekeke, Onyeanunam Ngozi, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Christopher, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Gillessen, Silke, Omlin, Aurelius, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, and UCL - (SLuc) Service d'urologie

Subjects
610 Medicine & health, 610 Medizin und Gesundheit
Published
2022
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25. Predictive Biomarkers of Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with IFNα ± Bevacizumab: Results from CALGB 90206 (Alliance)

Author

Nixon, Andrew B., primary, Halabi, Susan, additional, Liu, Yingmiao, additional, Starr, Mark D., additional, Brady, John C., additional, Shterev, Ivo, additional, Luo, Bin, additional, Hurwitz, Herbert I., additional, Febbo, Phillip G., additional, Rini, Brian I., additional, Beltran, Himisha, additional, Small, Eric J., additional, Morris, Michael J., additional, and George, Daniel J., additional

Published
2021
Full Text
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26. Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial

Author

Halabi, Susan, Yang, Qian, Carmack, Andrea, Zhang, Shiqi, Foo, Wen-Chi, Eisen, Tim, Stadler, Walter, Jones, Robert J., Garcia, Jorge, Picus, Joel, Hawkins, Robert, Hainsworth, John, Kollmannsberger, Christian, Logan, Theodore, Puzanov, Igor, Pickering, Lisa, Ryan, Christopher, Protheroe, Andrew, George, Daniel, and Armstrong, Andrew

Abstract

Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intentionto- treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor-risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.

Published
2021

27. Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19.

Author

Schmidt, Andrew L., Tucker, Matthew D., Bakouny, Ziad, Labaki, Chris, Hsu, Chih-Yuan, Shyr, Yu, Armstrong, Andrew J., Beer, Tomasz M., Bijjula, Ragneel R., Bilen, Mehmet A., Connell, Cindy F., Dawsey, Scott Joseph, Faller, Bryan, Gao, Xin, Gartrell, Benjamin A., Gill, David, Gulati, Shuchi, Halabi, Susan, Hwang, Clara, and Joshi, Monika

Published
2021
Full Text
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28. Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021

Author

Silke Gillessen, Andrew Armstrong, Gert Attard, Tomasz M. Beer, Himisha Beltran, Anders Bjartell, Alberto Bossi, Alberto Briganti, Robert G. Bristow, Muhammad Bulbul, Orazio Caffo, Kim N. Chi, Caroline S. Clarke, Noel Clarke, Ian D. Davis, Johann S. de Bono, Ignacio Duran, Ros Eeles, Eleni Efstathiou, Jason Efstathiou, Onyeanunam Ngozi Ekeke, Christopher P. Evans, Stefano Fanti, Felix Y. Feng, Karim Fizazi, Mark Frydenberg, Dan George, Martin Gleave, Susan Halabi, Daniel Heinrich, Celesta Higano, Michael S. Hofman, Maha Hussain, Nick James, Robert Jones, Ravindran Kanesvaran, Raja B. Khauli, Laurence Klotz, Raya Leibowitz, Chris Logothetis, Fernando Maluf, Robin Millman, Alicia K. Morgans, Michael J. Morris, Nicolas Mottet, Hind Mrabti, Declan G. Murphy, Vedang Murthy, William K. Oh, Piet Ost, Joe M. O'Sullivan, Anwar R. Padhani, Chris Parker, Darren M.C. Poon, Colin C. Pritchard, Danny M. Rabah, Dana Rathkopf, Rob E. Reiter, Mark Rubin, Charles J. Ryan, Fred Saad, Juan P. Sade, Oliver Sartor, Howard I. Scher, Neal Shore, Iwona Skoneczna, Eric Small, Matthew Smith, Howard Soule, Daniel E. Spratt, Cora N. Sternberg, Hiroyoshi Suzuki, Christopher Sweeney, Matthew R. Sydes, Mary-Ellen Taplin, Derya Tilki, Bertrand Tombal, Levent Türkeri, Hiroji Uemura, Hirotsugu Uemura, Inge van Oort, Kosj Yamoah, Dingwei Ye, Almudena Zapatero, Aurelius Omlin, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Acibadem University Dspace, Gillessen, Silke, Armstrong, Andrew, Attard, Gert, Beer, Tomasz M, Beltran, Himisha, Bjartell, Ander, Bossi, Alberto, Briganti, Alberto, Bristow, Robert G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline S, Clarke, Noel, Davis, Ian D, de Bono, Johann S, Duran, Ignacio, Eeles, Ro, Efstathiou, Eleni, Efstathiou, Jason, Ekeke, Onyeanunam Ngozi, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celesta, Hofman, Michael S, Hussain, Maha, James, Nick, Jones, Robert, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Chri, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicola, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Chri, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Rob E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan P, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel E, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew R, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Omlin, Aurelius, Gillessen, S., Armstron, A., Attard, G., Beer, T.M., Beltran, H., Bjartell, A., Bossi, A., Briganti, A., Bristow, R.G., Bulbul, M., Caffo, O., Chi, K.N., Clarke, C.S., Clarke, N., Davis, I.D., de Bono, J.S., Duran, I., Eeles, R., Efstathiou, E., Efstathiou, J., Ekeke, O.N., Evans, C.P., Fanti, S., Feng, F.Y., Fizazi, K., Frydenberg, M., George, D., Gleave, M., Halabi, S., Heinrich, D., Higano, C., Hofman, M.S., Hussain, M., James, N., Jones, R., Kanesvaran, R., Khauli, R.B., Klotz, L., Leibowitz, R., Logothetis, C., Maluf, F., Millman, R., Morgans, A.K., Morris, M.J., Mottet, N., Mrabti, H., Murphy, D.G., Murthy, V., Oh, W.K., Ost, P., O'Sullivan, J.M., Padhani, A.R., Parker, C., Poon, D.M.C., Pritchard, C.C., Rabah, D.M., Rathkopf, D., Reiter, R.E., Rubin, M., Ryan, C.J., Saad, F., Sade, J.P., Sartor, O., Scher, H.I., Shore, N., Skoneczna, I., Small, E., Smith, M., Soule, H., Spratt, D.E., Sternberg, C.N., Suzuki, H., Sweeney, C., Sydes, M.R., Taplin, M.E., Tombal, B., Türkeri, L., Uemura, H., van Oort, I., Yamoah, K., Ye, D., Zapatero, A., Omlin, A., Koç University Hospital, and School of Medicine

Subjects
Male, Consensus, Urology, education, Lu-177-PSMA therapy, Consensu, Hormone-sensitive prostate cancer, Imaging, SDG 3 - Good Health and Well-being, Genetic, Lu-PSMA therapy, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Genetics, Humans, Castration-resistant prostate cancer, Tumour genomic profiling, Manchester Cancer Research Centre, Advanced prostate cancer, ResearchInstitutes_Networks_Beacons/mcrc, PARP inhibition, 177Lu-PSMA therapy, Next-generation sequencing, Prostate cancer treatment, Prostatic Neoplasms, Urology and nephrology, (177)Lu-PSMA therapy, Human
Abstract

Background: innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. Objective: to present the voting results from APCCC 2021. Design, setting, and participants: the experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. Results and limitations: the voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: these voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. Patient summary: the Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making., National Health and Medical Research Council (NHMRC) Practitioner Fellowship; Prostate Cancer Foundation; Peter MacCallum Foundation; NHMRC Investigator Grant

Published
2022

29. Corrigendum to 'What Experts Think About Prostate Cancer Management During the COVID-19 Pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021' [Eur Urol 82(1):6–11]

Author

Fabio Turco, Andrew Armstrong, Gerhardt Attard, Tomasz M. Beer, Himisha Beltran, Anders Bjartell, Alberto Bossi, Alberto Briganti, Rob G. Bristow, Muhammad Bulbul, Orazio Caffo, Kim N. Chi, Caroline Clarke, Noel Clarke, Ian D. Davis, Johann de Bono, Ignacio Duran, Ros Eeles, Eleni Efstathiou, Jason Efstathiou, Christopher P. Evans, Stefano Fanti, Felix Y. Feng, Karim Fizazi, Mark Frydenberg, Dan George, Martin Gleave, Susan Halabi, Daniel Heinrich, Celestia Higano, Michael S. Hofman, Maha Hussain, Nicholas James, Rob Jones, Ravindran Kanesvaran, Raja B. Khauli, Laurence Klotz, Raya Leibowitz, Christopher Logothetis, Fernando Maluf, Robin Millman, Alicia K. Morgans, Michael J. Morris, Nicolas Mottet, Hind Mrabti, Declan G. Murphy, Vedang Murthy, William K. Oh, Onyeanunam Ngozi Ekeke, Piet Ost, Joe M. O'Sullivan, Anwar R. Padhani, Christopher Parker, Darren M.C. Poon, Colin C. Pritchard, Danny M. Rabah, Dana Rathkopf, Robert E. Reiter, Mark Rubin, Charles J. Ryan, Fred Saad, Juan Pablo Sade, Oliver Sartor, Howard I. Scher, Neal Shore, Iwona Skoneczna, Eric Small, Matthew Smith, Howard Soule, Daniel Spratt, Cora N. Sternberg, Hiroyoshi Suzuki, Christopher Sweeney, Matthew Sydes, Mary-Ellen Taplin, Derya Tilki, Bertrand Tombal, Levent Türkeri, Hiroji Uemura, Hirotsugu Uemura, Inge van Oort, Kosj Yamoah, Dingwei Ye, Almudena Zapatero, Silke Gillessen, Aurelius Omlin, Turco, Fabio, Armstrong, Andrew, Attard, Gerhardt, Beer, Tomasz M, Beltran, Himisha, Bjartell, Ander, Bossi, Alberto, Briganti, Alberto, Bristow, Rob G, Bulbul, Muhammad, Caffo, Orazio, Chi, Kim N, Clarke, Caroline, Clarke, Noel, Davis, Ian D, de Bono, Johann, Duran, Ignacio, Eeles, Ro, Efstathiou, Eleni, Efstathiou, Jason, Evans, Christopher P, Fanti, Stefano, Feng, Felix Y, Fizazi, Karim, Frydenberg, Mark, George, Dan, Gleave, Martin, Halabi, Susan, Heinrich, Daniel, Higano, Celestia, Hofman, Michael S, Hussain, Maha, James, Nichola, Jones, Rob, Kanesvaran, Ravindran, Khauli, Raja B, Klotz, Laurence, Leibowitz, Raya, Logothetis, Christopher, Maluf, Fernando, Millman, Robin, Morgans, Alicia K, Morris, Michael J, Mottet, Nicola, Mrabti, Hind, Murphy, Declan G, Murthy, Vedang, Oh, William K, Ekeke, Onyeanunam Ngozi, Ost, Piet, O'Sullivan, Joe M, Padhani, Anwar R, Parker, Christopher, Poon, Darren M C, Pritchard, Colin C, Rabah, Danny M, Rathkopf, Dana, Reiter, Robert E, Rubin, Mark, Ryan, Charles J, Saad, Fred, Sade, Juan Pablo, Sartor, Oliver, Scher, Howard I, Shore, Neal, Skoneczna, Iwona, Small, Eric, Smith, Matthew, Soule, Howard, Spratt, Daniel, Sternberg, Cora N, Suzuki, Hiroyoshi, Sweeney, Christopher, Sydes, Matthew, Taplin, Mary-Ellen, Tilki, Derya, Tombal, Bertrand, Türkeri, Levent, Uemura, Hiroji, Uemura, Hirotsugu, van Oort, Inge, Yamoah, Kosj, Ye, Dingwei, Zapatero, Almudena, Gillessen, Silke, and Omlin, Aurelius

Subjects
Urology, Prostate cancer Prostate cancer management COVID-19 pandemic COVID-19 vaccine COVID-19 boost injection Telemedicine
Abstract

Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic. There was a consensus for full COVID-19 vaccination and booster injection in APC patients. Furthermore, the voting results indicate that the expert’s treatment recommendations are influenced by the vaccination status: the COVID-19 pandemic altered management of APC patients for 70% of the panellists before the vaccination was available but only for 25% of panellists for fully vaccinated patients. Most experts (71%) were less likely to use docetaxel and abiraterone in unvaccinated patients with metastatic hormone-sensitive prostate cancer. For fully vaccinated patients with high-risk localised prostate cancer, there was a consensus (77%) to follow the usual treatment schedule, whereas in unvaccinated patients, 55% of the panel members voted for deferring radiation therapy. Finally, there was a strong consensus for the use of telemedicine for monitoring APC patients. Patient summary In the Advanced Prostate Cancer Consensus Conference 2021, the panellists reached a consensus regarding the recommendation of the COVID-19 vaccine in prostate cancer patients and use of telemedicine for monitoring these patients.

Published
2022

30. Androgen production, uptake, and conversion (APUC) genes define prostate cancer patients with distinct clinical outcomes.

Author

Bergom HE, Boytim E, McSweeney S, Sadeghipour N, Elliott A, Passow R, Toye E, Li X, Likasitwatanakul P, Geynisman DM, Dehm SM, Halabi S, Sharifi N, Antonarakis ES, Ryan CJ, and Hwang J

Abstract

Background: Prostate cancer (PC) is driven by aberrant signaling of the androgen receptor (AR) or its ligands, and androgen deprivation therapies (ADT) are a cornerstone of treatment. ADT responsiveness may be associated with germline alterations in genes that regulate androgen production, uptake, and conversion (APUC)., Methods: We analyzed whole-exome sequencing (WES) and whole transcriptome sequencing (WTS) data from prostate tissues (SU2C/PCF, TCGA, GETx). We also interrogated the Caris POA DNA (592-gene/whole exome) and RNA (whole transcriptome) NGS databases. Algorithm for Linking Activity Networks (ALAN) was used to quantify all pairwise gene-to-gene associations. Real-world overall survival (OS) was determined from insurance claims data using Kaplan-Meier estimates., Results: Six APUC genes (HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, CYP17A1) exhibited coalescent gene behavior in a cohort of metastatic tumors (n = 208). In the Caris POA dataset, the 6 APUC genes (APUC-6) exhibited robust clustering in primary prostate (n = 4,490) and metastatic (n = 2,593) biopsies. Surprisingly, tumors with elevated APUC-6 expression had statically lower expression of AR, AR-V7, and AR signaling scores suggesting ligand-driven disease biology. APUC-6 genes instead associated with the expression of alternative steroid hormone receptors, ESR1/2 and PGR. We used RNA expression of AR or APUC-6 genes to define two subgroups of tumors with differential association with hallmark pathways and cell surface targets., Conclusions: The APUC-6 high/AR-low tumors represented a subgroup of patients with good clinical outcomes in contrast to the AR-high or neuroendocrine prostate cancers. Altogether, measuring the aggregate expression of APUC-6 genes in current genomic tests identifies PCs that are ligand- (rather than AR-) driven and require distinct therapeutic strategies., Funding: NCI/NIH 1R37CA288972-01, NCI Cancer Center Support P30 CA077598, DOD W81XWH-22-2-0025, R01 CA249279.

Published
2024
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31. Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials.

Author

Hong H, Friedland A, Hu M, Anstrom KJ, Halabi S, McKinnon JE, Amaravadi R, Rojas-Serrano J, Abella BS, Portillo-Vázquez AM, Woods CW, Hernandez AF, Boulware DR, Naggie S, and Rajasingham R

Subjects
Humans, COVID-19 Drug Treatment, Health Personnel, Hydroxychloroquine adverse effects, Hydroxychloroquine pharmacology, SARS-CoV-2, Pre-Exposure Prophylaxis, COVID-19 prevention & control
Abstract

Objective: We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs)., Data Sources: PubMed and EMBASE databases were searched to identify randomised trials studying HCQ., Study Selection: Ten RCTs were identified (n=5079 participants)., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written., Main Outcomes: The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection., Results: Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73)., Conclusions and Relevance: Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events., Prospero Registration Number: CRD42021285093., Competing Interests: Competing interests: All authors except BSA reported no financial relationship with commercial interest. BSA has received NIH funds for COVID-19-related research and holds equity in VOC Health, a start-up company that is developing novel COVID-19 testing., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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32. Predictive Biomarkers of Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with IFNα ± Bevacizumab: Results from CALGB 90206 (Alliance).

Author

Nixon AB, Halabi S, Liu Y, Starr MD, Brady JC, Shterev I, Luo B, Hurwitz HI, Febbo PG, Rini BI, Beltran H, Small EJ, Morris MJ, and George DJ

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab adverse effects, Biomarkers, Disease-Free Survival, Genotype, Humans, Interferon-alpha administration & dosage, Interleukin-6, Phenotype, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell mortality, Kidney Neoplasms pathology
Abstract

Purpose: CALGB 90206 was a phase III trial of 732 patients with metastatic renal cell carcinoma (mRCC) comparing bevacizumab plus IFNα (BEV + IFN) with IFNα alone (IFN). No difference in overall survival (OS) was observed. Baseline samples were analyzed to identify predictive biomarkers for survival benefit., Patients and Methods: A total of 32 biomarkers were assessed in 498 consenting patients randomly assigned into training (n = 279) and testing (n = 219) sets. The proportional hazards model was used to test for treatment arm and biomarker interactions of OS. The estimated coefficients from the training set were used to compute a risk score for each patient and to classify patients by risk in the testing set. The resulting model was assessed for predictive accuracy using the time-dependent area under the ROC curve (tAUROC)., Results: A statistically significant three-way interaction between IL6, hepatocyte growth factor (HGF), and bevacizumab treatment was observed in the training set and confirmed in the testing set (P < 0.0001). The model based on IL6, HGF, and bevacizumab treatment was predictive of OS (P < 0.001), with the high- and low-risk groups having a median OS of 10.2 [95% confidence interval (CI), 8.0-13.8] and 34.3 (95% CI, 28.5-40.5) months, respectively. The average tAUROC for the final model of OS based on 100 randomly split testing sets was 0.78 (first, third quartiles = 0.77, 0.79)., Conclusions: IL6 and HGF are potential predictive biomarkers of OS benefit from BEV + IFN in patients with mRCC. The model based on key biological and clinical factors demonstrated predictive efficacy for OS. These markers warrant further validation in future anti-VEGF and immunotherapy in mRCC trials. See related commentaries by Mishkin and Kohn, p. 2722 and George and Bertagnolli, p. 2725., (©2021 American Association for Cancer Research.)

Published
2022
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33. Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial.

Author

Halabi S, Yang Q, Carmack A, Zhang S, Foo WC, Eisen T, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, George DJ, and Armstrong AJ

Abstract

Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.

Published
2021
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