Review
Health Care Sciences & Services
Fernando Lopez-Campos, Antonio Conde-Moreno, Marta Barrado Los Arcos, Antonio Gomez-Caamano, Raquel Garcia-Gomez, Asuncion Hervas Moron
Summary: The combination of ADT with apalutamide, enzalutamide, and darolutamide has shown significant clinical benefits for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC), including improved overall survival (OS). Therefore, these approaches are now considered standard of care and included in treatment guidelines for nmCRPC patients.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Correction
Medicine, General & Internal
Karim Fizazi, Neal Shore, Teuvo L. Tammela, Albertas Ulys, Egils Vjaters, Sergey Polyakov, Mindaugas Jievaltas, Murilo Luz, Boris Alekseev, Iris Kuss, Christian Kappeler, Amir Snapir, Toni Sarapohja, Matthew R. Smith
Summary: This article points out incorrect data regarding the application of Darolutamide in nonmetastatic, castration-resistant prostate cancer.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Felix Y. Feng, Shibu Thomas, Fred Saad, Michael Gormley, Margaret K. Yu, Deborah S. Ricci, Brendan Rooney, Sabine Brookman-May, Sharon McCarthy, David Olmos, Simon Chowdhury, Boris Hadaschik, Yang Liu, Elai Davicioni, Matthew R. Smith, Eric J. Small
Summary: The GC score and basal-luminal subtype derived from archived tumor specimens could be potential biomarkers for predicting response to apalutamide+ADT in nmCRPC patients. Although the addition of apalutamide to ADT was beneficial overall, higher-risk and luminal subtypes appeared to benefit most.
Article
Oncology
Emmanuel S. Antonarakis, Sumit K. Subudhi, Christopher M. Pieczonka, Lawrence I. Karsh, David I. Quinn, Jason M. Hafron, Helen M. Wilfehrt, Matthew Harmon, Nadeem A. Sheikh, Neal D. Shore, Daniel P. Petrylak
Summary: The purpose of this study was to investigate the impact of sequential or concurrent administration of androgen receptor-targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC). The results showed that the median OS remained consistent regardless of whether the agents were administered sequentially or concurrently, and sipuleucel-T induced an immunologic prime-boost effect after initial exposure, even when combined with ARTAs.
CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Fred Saad, Martin Boegemann, Kazuhiro Suzuki, Neal Shore
Summary: Nonmetastatic castration-resistant prostate cancer (nmCRPC) is characterized by rising PSA levels despite castration therapy, and patients are at risk of developing metastatic disease and cancer-related symptoms. Treatment decisions for nmCRPC patients should consider the balance between clinical benefits and potential adverse events of second-generation androgen receptor inhibitors to delay metastases and prolong survival.
PROSTATE CANCER AND PROSTATIC DISEASES
(2021)
Article
Oncology
David F. Penson, Andrew J. Armstrong, Raoul S. Concepcion, Neeraj Agarwal, Carl A. Olsson, Lawrence Karsh, Curtis J. Dunshee, William Duggan, Qi Shen, Jennifer Sugg, Gabriel P. Haas, Celestia S. Higano
Summary: Enzalutamide demonstrated a significant reduction in the risk of disease progression or death compared to Bicalutamide in patients with nonmetastatic castration-resistant prostate cancer, and also lowered the risk of prostate-specific antigen progression in these patients.
PROSTATE CANCER AND PROSTATIC DISEASES
(2022)
Article
Medicine, General & Internal
Kelli M. Rasmussen, Vikas Patil, Chunyang Li, Christina Yong, Sreevalsa Appukkutan, Jamie Partridge Grossman, Jay Jhaveri, Ahmad S. Halwani
Summary: This study examines clinical outcomes by race and ethnicity in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) within the US Veterans Health Administration. The results suggest that there are differences in outcomes by race and ethnicity, and Black and Hispanic men may have considerably improved outcomes when treated in an equal-access setting.
Review
Pharmacology & Pharmacy
Arnaldo Figueiredo, Luis Costa, Maria Joaquina Mauricio, Luis Figueira, Rodrigo Ramos, Carlos Martins-da-Silva
Summary: Prostate carcinoma is a highly prevalent and diverse disease. Nonmetastatic castration-resistant prostate cancer is a transient stage that most patients eventually progress to metastatic lesions. Treatment decisions for this population are challenging due to disease heterogeneity.
CLINICAL DRUG INVESTIGATION
(2022)
Article
Oncology
Joan Carles, Rafael A. Medina-Lopez, Javier Puente, Alvaro Gomez-Ferrer, Javier Casas Nebra, Maria Isabel Saez Medina, Maria J. Ribal, Alfredo Rodriguez Antolin, Jose Luis Alvarez-Ossorio, Jose Francisco Suarez Novo, Cristina Moretones Agut, Shankar Srinivasan, Jorge Ortiz, Karim Fizazi
Summary: In the Phase III ARAMIS study, darolutamide significantly prolonged metastasis-free survival in patients with high-risk nonmetastatic castration-resistant prostate cancer. In this post hoc analysis, Spanish participants treated with darolutamide had a longer metastasis-free survival compared to those treated with placebo, with similar treatment-emergent adverse events.
Review
Oncology
Carlo Cattrini, Orazio Caffo, Ugo De Giorgi, Alessia Mennitto, Alessandra Gennari, David Olmos, Elena Castro
Summary: This review discusses the use of apalutamide, darolutamide, and enzalutamide in patients with nmCRPC and the clinical implications of novel imaging techniques for treatment selection.
Review
Oncology
Alessandro Rizzo, Marco Oderda, Veronica Mollica, Sara Merler, Franco Morelli, Benedetta Fragomeno, Elena Taveri, Giulia Sorgentoni, Matteo Santoni, Francesco Massari
Summary: This study reviewed the use of several novel AR inhibitors in patients with nmCRPC and evaluated the overall survival, incidence and risk of adverse events, adverse-events-related death, and adverse-events-related treatment discontinuation. The use of new hormonal agents improved overall survival despite the increased risk of adverse events. Therefore, careful consideration of the expected adverse events, patients' comorbidities, and maintenance of quality of life is necessary in the decision-making process.
Article
Urology & Nephrology
Susan Halabi, Shan Jiang, Emi Terasawa, Viviana Garcia-Horton, Rajeev Ayyagari, A. Reginald Waldeck, Neal Shore
Summary: This study compared the safety and efficacy of darolutamide vs apalutamide, and darolutamide vs enzalutamide in nonmetastatic castration-resistant prostate cancer through matching-adjusted indirect comparisons. While there were no differences in metastasis-free survival, darolutamide showed lower rates of certain adverse events compared to apalutamide and enzalutamide, suggesting a more favorable safety and tolerability profile.
JOURNAL OF UROLOGY
(2021)
Article
Multidisciplinary Sciences
Madhav Prasad Yadav, Sanjana Ballal, Ranjit Kumar Sahoo, Madhavi Tripathi, Nishikant Avinash Damle, Shamim Ahmed Shamim, Rakesh Kumar, Amlesh Seth, Chandrasekhar Bal
Summary: This study focused on the long-term outcomes of mCRPC patients treated with Lu-177-PSMA-617 RLT. Results showed favorable efficacy with potential for prolonged survival, but further research on prognostic factors within the patient cohort is needed.
Article
Oncology
Kim N. Chi, Dana Rathkopf, Matthew R. Smith, Eleni Efstathiou, Gerhardt Attard, David Olmos, Ji Youl Lee, Eric J. Small, Andrea J. Pereira De Santana Gomes, Guilhem Roubaud, Marniza Saad, Bogdan Zurawski, Valerii Sakalo, Gary E. Mason, Peter Francis, George Wang Ms, Daphne Wu, Brooke Diorio, Angela Lopez-Gitlitz, Shahneen Sandhu
Summary: This study investigated the efficacy of niraparib in combination with abiraterone acetate plus prednisone in patients with mCRPC and HRR gene alterations. The results showed that the combination therapy significantly prolonged radiographic progression-free survival compared to abiraterone acetate plus prednisone alone. The treatment was well tolerated with manageable adverse events.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Medicine, General & Internal
Oliver Sartor, Johann de Bono, Kim N. Chi, Karim Fizazi, Ken Herrmann, Kambiz Rahbar, Scott T. Tagawa, Luke T. Nordquist, Nitin Vaishampayan, Ghassan El-Haddad, Chandler H. Park, Tomasz M. Beer, Alison Armour, Wendy J. Perez-Contreras, Michelle DeSilvio, Euloge Kpamegan, Germo Gericke, Richard A. Messmann, Michael J. Morris, Bernd J. Krause
Summary: The radioligand therapy with Lu-177-PSMA-617 prolonged both imaging-based progression-free survival and overall survival in patients with PSMA-positive metastatic castration-resistant prostate cancer when added to standard care. Adverse events were more common with Lu-177-PSMA-617 but did not significantly impact quality of life.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Meghali Goswami, Gege Gui, Laura W. Dillon, Katherine E. Lindblad, Julie Thompson, Janet Valdez, Dong-Yun Kim, Jack Y. Ghannam, Karolyn A. Oetjen, Christin B. Destefano, Dana M. Smith, Hanna Tekleab, Yeusheng Li, Pradeep Dagur, Thomas Hughes, Jennifer L. Marte, Jaydira del Rivero, Joanna Klubo-Gwiezdzinksa, James L. Gulley, Katherine R. Calvo, Catherine Lai, Christopher S. Hourigan
Summary: This study aimed to investigate the feasibility and efficacy of the combination of PD-1 blockade and hypomethylating therapy in patients with R-AML. The results showed that this combination therapy achieved disease stability or better response in some patients. Moreover, clonal T cell expansions and immunological changes were observed during treatment, which may be associated with treatment-related adverse events.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Nicholas P. Tschernia, James L. Gulley
Summary: Cancer immunotherapy with monoclonal antibodies targeting immune checkpoints has significantly changed the landscape of cancer treatment. However, only a minority of patients benefit considerably from these treatments, attributed to factors like the immune-suppressive tumor microenvironment and TGF-beta. Therefore, investigating and developing inhibitors targeting TGF-beta in combination with immune checkpoint inhibitors is crucial for improving patient outcomes.
Review
Medicine, Research & Experimental
Sofia R. Gameiro, Julius Strauss, James L. Gulley, Jeffrey Schlom
Summary: Bintrafusp alfa is a novel bifunctional agent designed to target the immune system and tumor microenvironment, with promising results in HPV-associated malignancies. Clinical studies have shown superior efficacy of bintrafusp alfa in combination with HPV therapeutic vaccine and IL-12 immunocytokine compared to standard-of-care therapies.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Oncology
Arun Rajan, Jhanelle E. Gray, Siddhartha Devarakonda, Ruemu Birhiray, Borys Korchin, Erika Menius, Renee N. Donahue, Jeffrey Schlom, James L. Gulley
Summary: CV301 in combination with PD-1 inhibitors is safe and clinically active in advanced NSCLC patients, without an increased frequency or severity of immune-related adverse events.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Mary Helen Barcellos-Hoff, James L. Gulley
Summary: Despite the increasing number of TGFI3 inhibitors tested in cancer patients, there has been no clinical benefit achieved yet. The main obstacle to effective TGFI3 inhibition is the diverse mechanisms by which TGFI3 promotes tumor growth. TGFI3 is involved in regulating DNA repair and immune suppression, which can be used to synergize genotoxic therapy and immunotherapy for the benefit of cancer patients.
CLINICAL CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Cody J. Peer, Keith T. Schmidt, Oluwatobi Arisa, William J. Richardson, Koosha Paydary, Daniel A. Goldstein, James L. Gulley, William D. Figg, Mark J. Ratain
Summary: Atezolizumab, a humanized monoclonal antibody against PD-L1, was approved in 2016. Standard dose regimens result in high plasma concentrations, indicating the need for alternative dosing strategies to reduce exposure burden.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Oncology
Alexander Spira, Michael S. Wertheim, Edward J. Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L. Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L. Gulley, Scott Kopetz
Summary: A phase I study on bintrafusp alfa in heavily pretreated patients with colorectal cancer showed promising early signs of clinical efficacy and manageable safety profile.
Article
Oncology
Fabrice Barlesi, Nicolas Isambert, Enriqueta Felip, Byoung Chul Cho, Dae Ho Lee, Julio Peguero, Guy Jerusalem, Nicolas Penel, Esma Saada-Bouzid, Pilar Garrido, Christoph Helwig, George Locke, Laureen S. Ojalvo, James L. Gulley
Summary: Bintrafusp alfa showed some clinical activity and a manageable safety profile in heavily pretreated NSCLC patients.
Article
Oncology
Margaret E. Gatti-Mays, Nicholas P. Tschernia, Julius Strauss, Ravi A. Madan, Fatima H. Karzai, Marijo Bilusic, Jason Redman, Houssein Abdul Sater, Charalampos S. Floudas, Nicole J. Toney, Renee N. Donahue, Caroline Jochems, Jennifer L. Marte, Deneise Francis, Sheri McMahon, Elizabeth Lamping, Lisa Cordes, Jeffrey Schlom, James L. Gulley
Summary: The results of this study showed that biweekly NHS-IL12 treatment was safe for patients with advanced cancers. NHS-IL12 is a first-in-class fusion protein used in this trial. Patients received NHS-IL12 every two weeks, and the results demonstrated stable disease status for the patients.
Article
Oncology
Emerson A. Lim, Michael T. Schweizer, Kim N. Chi, Rahul Aggarwal, Neeraj Agarwal, James Gulley, Edward Attiyeh, James Greger, Shujian Wu, Pharavee Jaiprasart, John Loffredo, Nibedita Bandyopadhyay, Hong Xie, Aaron R. Hansen
Summary: PSMA expression is maintained in all stages of prostate cancer. In a phase 1 study, a bispecific antibody targeting PSMA-expressing tumor cells and CD3-expressing T cells showed manageable cytokine release syndrome and temporary decline in PSA in patients with metastatic castration-resistant prostate cancer. Treatment-related deaths and radiographic responses were not observed. PSMA is a potential therapeutic target for T-cell redirection in prostate cancer.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Oncology
Michael B. Atkins, Paolo A. Ascierto, David Feltquate, James L. Gulley, Douglas B. Johnson, Nikhil Khushalani, Jeffrey Sosman, Timonthy A. Yap, Harriet Kluger, Ryan J. Sullivan, Hussein Tawbi
Summary: Immunotherapy alone does not work for all tumors, so combining it with signal transduction inhibitors, such as antiangiogenic therapies, can enhance its effectiveness. Combination therapies with immunotherapy have shown improved antitumor activity in various solid tumor settings and have received regulatory approval for the treatment of several types of cancer. However, many patients still experience progression after combination treatment, highlighting the need for new strategies to address resistance to immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Ryan Chang, James L. Gulley, Lawrence Fong
Summary: Immunotherapies, such as immune checkpoint inhibitors and cellular therapies, have revolutionized cancer treatment, but the development of successful cancer vaccines remains challenging. Only two vaccines have shown improved survival in advanced disease: sipuleucel-T and talimogene laherparepvec, which target specific antigens and utilize tumors in situ to prime responses. In this review, we examine the challenges and opportunities in developing therapeutic cancer vaccines.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Meeting Abstract
Oncology
Mohammad O. Atiq, Shruti U. Gandhy, Fatima Karzai, Munjid Al Harthy, Gang Chen, Marijo Bilusic, David James VanderWeele, Elias Bin Aris Chandran, Lisa M. Cordes, Helen Owens, Anna Couvillon, Amy Hankin, Monique Williams, William Douglas Figg, Peter L. Choyke, Liza Lindenberg, Esther Mena, William L. Dahut, James L. Gulley, Ravi Amrit Madan
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Mohammad O. Atiq, Elias Bin Aris Chandran, Luke Meininger, Fatima Karzai, Marijo Bilusic, Jennifer L. Marte, Philip M. Arlen, Lisa M. Cordes, Julius Strauss, Jason Redman, Charalampos S. Floudas, Danielle M. Pastor, Helen Owens, Amy Hankin, Monique Williams, William Douglas Figg, William L. Dahut, Jeffrey Schlom, James L. Gulley, Ravi Amrit Madan
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Nirmal Choradia, James L. Gulley, Charalampos S. Floudas
JOURNAL OF CLINICAL ONCOLOGY
(2022)