المؤلفون: Patel, Sandip, Alonso-Gordoa, Teresa, Banerjee, Susana, Wang, Ding, Naidoo, Jarushka, Standifer, Nathan, Palmer, Doug, Cheng, Lin-Yang, Kourtesis, Panagiotis, Ascierto, Maria, Das, Mayukh, Diamond, Jennifer, Hellmann, Matthew, Carneiro, Benedito

المصدر: Journal for ImmunoTherapy of Cancer. 12(2)

مصطلحات موضوعية: Adaptive Immunity, Immunity, Innate, Natural Killer T-Cells, Programmed Cell Death 1 Receptor, Tumor Microenvironment, Female, Humans, Adolescent, Adult, Carcinoma, Non-Small-Cell Lung, Ligands, Lung Neoplasms, Tumor Microenvironment, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized

الوصف: BACKGROUND: The combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors. MAIN BODY: Immunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0-1, and 1-3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8+ T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif chemokine ligand 10) and CXCL11, and increased tumor infiltration of CD8+ and granzyme B+ cells were observed. CONCLUSIONS: Although efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME. TRIAL REGISTRATION NUMBER: NCT02671435.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2888m63bTest

المؤلفون: Gómez-Vecino, Aurora, Corchado-Cobos, Roberto, Blanco-Gómez, Adrián, García-Sancha, Natalia, Castillo-Lluva, Sonia, Martín-García, Ana, Mendiburu-Eliçabe, Marina, Prieto, Carlos, Ruiz-Pinto, Sara, Pita, Guillermo, Velasco-Ruiz, Alejandro, Patino-Alonso, Carmen, Galindo-Villardón, Purificación, Vera-Pedrosa, María, Jalife, José, Macías de Plasencia, Guillermo, Castellanos-Martín, Andrés, Sáez-Freire, María, Fraile-Martín, Susana, Rodrigues-Teixeira, Telmo, García-Macías, Carmen, Galvis-Jiménez, Julie, García-Sánchez, Asunción, Isidoro-García, María, Fuentes, Manuel, García-Cenador, María, García-Criado, Francisco, García-Hernández, Juan, Hernández-García, María, Cruz-Hernández, Juan, Rodríguez-Sánchez, César, García-Sancho, Alejandro, Pérez-López, Estefanía, Pérez-Martínez, Antonio, Gutiérrez-Larraya, Federico, Cartón, Antonio, García-Sáenz, José, Patiño-García, Ana, Martín, Miguel, Alonso-Gordoa, Teresa, Vulsteke, Christof, Croes, Lieselot, Hatse, Sigrid, Van Brussel, Thomas, Lambrechts, Diether, Wildiers, Hans, Chang, Hang, Holgado-Madruga, Marina, González-Neira, Anna, Sánchez, Pedro, Pérez Losada, Jesús, Mao, Jian-Hua

المصدر: Cells. 12(15)

مصطلحات موضوعية: anthracyclines, cardiotoxicity, complex genetic disease, intermediate molecular phenotypes, quantitative trait loci, Female, Animals, Mice, Cardiotoxicity, Anthracyclines, Genetic Markers, Antibiotics, Antineoplastic, Neoplasms, Phenotype

الوصف: Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4k2253n5Test

المؤلفون: Lamarca, Angela, Cives, Mauro, de Mestier, Louis, Crona, Joakim, Spada, Francesca, Öberg, Kjell, 1946, Pavel, Marianne, Alonso-Gordoa, Teresa

المصدر: World Journal of Gastroenterology. 27(10):976-989

مصطلحات موضوعية: Neuroendocrine tumour, Small bowel, Survey, Third-line, Advanced, Practice

الوصف: BACKGROUND Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence. AIM To understand current practice and rationale for decision-making by physicians in the 3(rd)-line setting by building an online survey. METHODS Weighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored. RESULTS Replies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3(rd)-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3(rd)-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4). CONCLUSION Everolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-440427Test
https://doi.org/10.3748/wjg.v27.i10.976Test

المؤلفون: Fernandez-Perez, Maria P, Perez-Navarro, Enrique, Alonso-Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vazquez-Estevez, Sergio, Gonzalez-del-Alba, Aranzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S, Mellado, Begona, Fernandez-Calvo, Ovidio, Mendez-Vidal, Maria J, Climent, Miguel A, Duran, Ignacio, Gallardo, Enrique, Rodriguez Sanchez, Angel, Santander, Carmen, Saez, Maria, Puente, Javier, Tudela, Julian, Martinez, Alberto, Lopez-Andreo, Maria J, Padilla, Jose, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gonzalez-Billalabeitia, Enrique

المصدر: Prostate , 83 (4) pp. 376-384. (2023)

مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, Urology & Nephrology, AR gain, AR-V7, CTCs, enzalutamide, prostate cancer, TMPRSS2-ERG, CIRCULATING TUMOR-CELLS, GENE STATUS, ANDROGEN RECEPTOR, CLINICAL-TRIALS, ABIRATERONE, SURVIVAL, SURROGATE, TMPRSS2, FUSION, MEN

الوصف: Background: There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). Methods: We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical–molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Results: Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. Conclusions: TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10164231/1/A%20correlative%20biomarker%20study%20and%20integrative%20prognostic%20model.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10164231Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10164231/1/A%20correlative%20biomarker%20study%20and%20integrative%20prognostic%20model.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10164231Test/

المؤلفون: Capdevila, Jaume, Hernando, Jorge, Teulé Vega, Àlex, Lopez, C., Garcia Carbonero, R., Benavent, M., Custodio, Ana, García Alvárez, Alejandro, Cubillo, A., Alonso, V., Carmona Bayonas, Alberto, Alonso Gordoa, Teresa, Crespo, Guillermo, Jiménez Fonseca, P., Blanco, M., Viudez, A., Casta, A. la, Sevilla, I., Segura, A., Llanos, M., Landolfi, Stefania, Nuciforo, Paolo, Manzano Mozo, José Luis

المصدر: Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

مصطلحات موضوعية: Neuroendocrinologia, Tumors, Neuroendocrinology

الوصف: Single immune checkpoint blockade has shown limited activity in patients with neuroendocrine neoplasms (NENs). Here the authors report the results of a phase II clinical trial of durvalumab (anti-PD-L1) and tremelimumab (anti CTLA-4) in patients with advanced NENs of gastroenteropancreatic and lung origin. Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

وصف الملف: 8 p.; application/pdf

العلاقة: Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-38611-5Test; Nature Communications, 2023, vol. 14, num. 1; https://doi.org/10.1038/s41467-023-38611-5Test; http://hdl.handle.net/2445/200909Test

الإتاحة: https://doi.org/10.1038/s41467-023-38611-5Test
http://hdl.handle.net/2445/200909Test

المؤلفون: Carmona-Bayonas, Alberto, Custodio, Ana, García Carbonero, Rocío, Capdevila Castillon, Jaume, Alonso-Gordoa, Teresa, Grande, Enrique

المساهمون: Institut Català de la Salut, Capdevila Castillón J Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Alonso Gordoa T Servicio de Oncología Médica, Hospital Universitario Ramón y Cajal, Madrid, Spain. Carmona Bayonas A Servicio de Oncología Médica, Hospital Universitario Morales Meseguer, Murcia, Spain. Custodio Carretero A Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain. García-Carbonero R Servicio de Oncología Médica, Hospital Universitario 12 de Octubre, Madrid, Spain. Grande Pulido E Servicio de Oncología Médica, MD Anderson Cancer Center, Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus

المصدر: Scientia

مصطلحات موضوعية: Tumors neuroendocrins - Tractament, Bronquis - Càncer - Tractament, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors, DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms, HEALTH CARE::Health Services Administration::Patient Care Management::Disease Management, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios, ATENCIÓN DE SALUD::administración de los servicios de salud::gestión de la atención al paciente::tratamiento de las enfermedades

الوصف: Diagnosis; Neuroendocrine; Therapy ; Diagnòstic; Neuroendocrí; Teràpia ; Diagnóstico; Neuroendocrino; Terapia ; Neuroendocrine neoplasms (NENs) are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise mainly due to an improvement on diagnostic techniques and awareness. Earlier detection, along with steadfast improvements in therapy, has led to better prognosis over time for advanced gastrointestinal and pancreatic neuroendocrine tumors. The aim of this guideline is to update evidence-based recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification, and therapeutic options, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are reviewed and discussed, and treatment algorithms to guide therapeutic decisions are provided.

وصف الملف: application/pdf

العلاقة: Clinical and Translational Oncology;25; https://doi.org/10.1007/s12094-023-03205-6Test; Capdevila Castillón J, Alonso Gordoa T, Carmona Bayonas A, Custodio Carretero A, García-Carbonero R, Grande Pulido E, et al. SEOM-GETNE clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2022). Clin Transl Oncol. 2023 Sep;25:2692–706.; https://hdl.handle.net/11351/10244Test; 000990922300001

الإتاحة: https://doi.org/10.1007/s12094-023-03205-6Test
https://hdl.handle.net/11351/10244Test

المؤلفون: Fernández-Pérez, M. P., Pérez-Navarro, Enrique, Alonso Gordoa, Teresa, Conteduca, Vicenza, Font Pous, Albert, Vázquez-Estévez, Sergio, González del Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado González, Begoña, Fernández-Calvo, Ovidio, Méndez-Vidal, María J., Climent, Miguel A., Durán, Ignacio, Gallardo, Enrique, Rodríguez Sánchez, Ángel, Santander, Carmen, Sáez, María Isabel, Puente Vázquez, Javier, Tudela, Julián, Martínez, Alberto, López-Andreo, María J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, García-Castellanos, Daniel, Attard, Gerhardt, Grande, Enrique, González-Billalabeitia, E.

المساهمون: Astellas Pharma, Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Fundación CRIS contra el Cáncer

مصطلحات موضوعية: Prostate cancer, AR gain, AR-V7, CTCs, TMPRSS2-ERG, Enzalutamide

الوصف: [Background] There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). ; [Methods] We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical–molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. ; [Results] Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. ; [Conclusions] TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers. ; The authors would like to acknowledge all the staff at SOGUG for their support to run the PREMIERE trial, Astellas for supporting this research, ISCIII from the Spanish Ministry of Health, and Cris Cancer Foundation for their support. This trial was ...

وصف الملف: application/pdf

العلاقة: Publisher's version; The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1002/pros.24469; https://doi.org/10.1002/pros.24469Test; Sí; The Prostate 83(4): 376-384 (2023); http://hdl.handle.net/10261/333013Test; http://dx.doi.org/10.13039/501100004948Test; http://dx.doi.org/10.13039/501100003751Test; http://dx.doi.org/10.13039/501100004587Test; 2-s2.0-85145039209; https://api.elsevier.com/content/abstract/scopus_id/85145039209Test

الإتاحة: https://doi.org/10.1002/pros.2446910.13039/50110000494810.13039/50110000375110.13039/501100004587Test
http://hdl.handle.net/10261/333013Test
https://api.elsevier.com/content/abstract/scopus_id/85145039209Test

المؤلفون: Grünwald, Viktor, Powles, Thomas, Kopyltsov, Evgeny, Kozlov, Vadim, Alonso-Gordoa, Teresa, Eto, Masatoshi, Hutson, Thomas, Motzer, Robert, Winquist, Eric, Maroto, Pablo, Keam, Bhumsuk, Procopio, Giuseppe, Wong, Shirley, Melichar, Bohuslav, Rolland, Frederic, Oya, Mototsugu, Rodriguez-Lopez, Karla, Saito, Kenichi, McKenzie, Jodi, Porta, Camillo

المصدر: European Urology Oncology ; volume 6, issue 4, page 437-446 ; ISSN 2588-9311

مصطلحات موضوعية: Urology, Radiology, Nuclear Medicine and imaging, Oncology, Surgery

الإتاحة: https://doi.org/10.1016/j.euo.2023.01.010Test
https://api.elsevier.com/content/article/PII:S2588931123000287?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2588931123000287?httpAccept=text/plainTest

المؤلفون: Patel, Sandip P, Alonso-Gordoa, Teresa, Banerjee, Susana, Wang, Ding, Naidoo, Jarushka, Standifer, Nathan E, Palmer, Doug C, Cheng, Lin-Yang, Kourtesis, Panagiotis, Ascierto, Maria L, Das, Mayukh, Diamond, Jennifer R, Hellmann, Matthew D, Carneiro, Benedito A

المصدر: Hematology/Oncology Articles

مصطلحات موضوعية: Female, Humans, Adolescent, Adult, Carcinoma, Non-Small-Cell Lung, Ligands, Lung Neoplasms, Tumor Microenvironment, Antibodies, Monoclonal, Humanized

الوصف: BACKGROUND: The combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors. MAIN BODY: Immunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0-1, and 1-3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8(+) T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif ...

العلاقة: https://scholarlycommons.henryford.com/hematologyoncology_articles/347Test; http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:38309722Test

الإتاحة: https://scholarlycommons.henryford.com/hematologyoncology_articles/347Test
http://sfxhosted.exlibrisgroup.com/hfhs?sid=Entrez:PubMed&id=pmid:38309722Test

المؤلفون: Esteban Villarrubia, Jorge, Alonso Gordoa, Teresa, Mellado-González, Begoña, Duran, Ignacio, Pinto, Alvaro, Sanchez, Alfredo, Font Pous, Albert, Vazquez-Estevez, Sergio, Puente, Javier, Grande, Enrique, Climent, Miguel Ángel, Maroto-Rey, Pablo, Perez-Gracia, Jose Luis, Ponce Aix, Santiago, Castellano, Daniel, Gonzalez-Billalabeitia, Enrique

المصدر: Journal of Clinical Oncology; 2024 Supplement 4, Vol. 42, pTPS238-TPS238, 235p