المؤلفون: Cordeiro de Lima, Vladmir C., Gelatti, Ana, Moura, José F.P., Fares, Aline F., de Castro, Gilberto, Mathias, Clarissa, Terra, Ricardo M., Werutsky, Gustavo, Corassa, Marcelo, Araújo, Luiz Henrique L., Cronenberger, Eduardo, Fujiki, Fernanda K., Reichow, Sandro, da Silva, Antônio Vinícius T., Reis, Tércia V., Padoan, Mônica Luciana A., Pacheco, Patrícia, Yamamura, Rosely, Kawamura, Caroline, Mascarenhas, Eldsamira, de Jesus, Rafaela G., Gössling, Gustavo, Baldotto, Clarissa

المساهمون: AstraZeneca

المصدر: JTO Clinical and Research Reports ; volume 5, issue 3, page 100646 ; ISSN 2666-3643

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.jtocrr.2024.100646Test
https://api.elsevier.com/content/article/PII:S266636432400016X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S266636432400016X?httpAccept=text/plainTest

المؤلفون: Mansfield, Aaron S., Herbst, Roy S., de Castro, Gilberto, Hui, Rina, Peled, Nir, Kim, Dong-Wan, Novello, Silvia, Satouchi, Miyako, Wu, Yi-Long, Garon, Edward B., Reck, Martin, Robinson, Andrew G., Samkari, Ayman, Piperdi, Bilal, Ebiana, Victoria, Lin, Jianxin, Mok, Tony S.K.

المساهمون: Kim, Dong-Wan

مصطلحات موضوعية: Brain metastases, Chemotherapy, Non‒small-cell lung cancer, PD-L1, Pembrolizumab

الوصف: Introduction: We retrospectively evaluated outcomes in patients with programmed death-ligand 1 (PD-L1)–positive NSCLC to determine whether baseline (i.e., at study enrollment) brain metastases were associated with the efficacy of pembrolizumab versus chemotherapy. Methods: We pooled the data for patients with previously treated or untreated PD-L1‒positive (tumor proportion score [TPS], ≥1%) advanced metastatic NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894). Patients received pembrolizumab (2 mg/kg, 10 mg/kg, or 200 mg every 3 wk or 10 mg/kg every 2 wk); chemotherapy was a comparator in all studies except KEYNOTE-001. All studies included patients with previously treated, stable brain metastases. Results: A total of 3170 patients were included, 293 (9.2%) with and 2877 (90.8%) without baseline brain metastases; median (range) follow-up at data cutoff was 12.9 (0.1‒43.7) months. Pembrolizumab improved overall survival versus chemotherapy in patients with or without baseline brain metastases: benefit was seen in patients with PD-L1 TPS greater than or equal to 50% (0.67 [95% confidence intervals (CI): 0.44‒1.02] and 0.66 [95% CI: 0.58‒0.76], respectively) and PD-L1 TPS ≥1% (0.83 [95% CI: 0.62‒1.10] and 0.78 [95% CI: 0.71‒0.85], respectively). Progression-free survival was improved, objective response rates were higher, and the duration of response was longer with pembrolizumab versus chemotherapy regardless of brain metastasis status. The incidence of treatment-related adverse events with pembrolizumab versus chemotherapy was 66.3% versus 84.4% in patients with brain metastases and 67.2% versus 88.3% in those without. Conclusions: Pembrolizumab monotherapy improved outcomes and was associated with fewer adverse events than chemotherapy in patients with treatment-naive and previously treated PD-L1‒positive advanced/metastatic NSCLC regardless of the presence of baseline treated, stable brain metastases. ; Y ; 1

العلاقة: JTO Clinical and Research Reports, Vol.2 No.8, p. 100205; https://hdl.handle.net/10371/195328Test; 2-s2.0-85112615261; 187863

الإتاحة: https://doi.org/10.1016/j.jtocrr.2021.100205Test
https://hdl.handle.net/10371/195328Test

المؤلفون: Bryl, Maciej, Zer, Alona, Timcheva, Constanta, Raja, Rajiv, Naicker, Kirsha, Scheuring, Urban, Walker, Jill, Mann, Helen, Chand, Vikram, Mok, Tony, Erman, Mustafa, Martin, Claudio, Syrigos, Konstantinos, Schmid, Peter, Rizvi, Naiyer A., de Castro, Gilberto, Vynnychenko, Ihor, Moiseyenko, Vladimir, Summers, Yvonne, Cheng, Ying, Yamamoto, Nobuyuki, Lee, Sung Yong

الوصف: © 2022 International Association for the Study of Lung CancerIntroduction: NEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC). Methods: Eligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg every 4 weeks until progression) plus tremelimumab (1 mg/kg every 4 weeks for up to four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (≥25% versus <25%), tumor histologic type, and smoking history. The amended primary end point was overall survival (OS) in patients with blood tumor mutational burden (bTMB) greater than or equal to 20 mutations per megabase (mut/Mb). Secondary end points included progression-free survival (PFS) in patients with bTMB greater than or equal to 20 mut/Mb and safety and tolerability in all treated patients. Results: As of June 24, 2019, 823 patients were randomized (intention-to-treat [ITT]); 512 (62%) were bTMB-evaluable, with 129 of 512 (25%) having bTMB greater than or equal to 20 mut/Mb (durvalumab plus tremelimumab [n = 69]; chemotherapy [n = 60]). Baseline characteristics were balanced in the intention-to-treat. Among patients with bTMB greater than or equal to 20 mut/Mb, OS improvement with durvalumab plus tremelimumab versus chemotherapy did not reach statistical significance (hazard ratio 0.71 [95% confidence interval: 0.49–1.05; p = 0.081]; median OS, 11.7 versus 9.1 months); the hazard ratio for PFS was 0.77 (95% confidence interval, 0.51–1.15; median PFS, 4.2 versus 5.1 months). In the overall safety population, incidence of grade 3 or 4 treatment-related adverse events was 20.7% (durvalumab plus tremelimumab) and 33.6% (chemotherapy). Conclusions: NEPTUNE did not meet its primary end point of improved OS with durvalumab plus tremelimumab versus chemotherapy in patients with mNSCLC and bTMB greater than or equal to 20 mut/Mb. Despite the amended study design, with a resultant small ...

العلاقة: 628627cd-ce6d-41ca-943d-de329292bc31; https://avesis.hacettepe.edu.tr/publication/details/628627cd-ce6d-41ca-943d-de329292bc31/oaiTest

الإتاحة: https://doi.org/10.1016/j.jtho.2022.09.223Test
https://avesis.hacettepe.edu.tr/publication/details/628627cd-ce6d-41ca-943d-de329292bc31/oaiTest

المؤلفون: de Castro, Gilberto, Souza, Fabiano Hahn, Lima, Júlia, Bernardi, Luis Pedro, Teixeira, Carlos Henrique Andrade, Prado, Gustavo Faibischew

المصدر: JTO Clinical and Research Reports ; volume 4, issue 12, page 100580 ; ISSN 2666-3643

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.jtocrr.2023.100580Test
https://api.elsevier.com/content/article/PII:S2666364323001236?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666364323001236?httpAccept=text/plainTest

المؤلفون: de Castro, Gilberto, Rizvi, Naiyer A., Schmid, Peter, Syrigos, Konstantinos, Martin, Claudio, Yamamoto, Nobuyuki, Cheng, Ying, Moiseyenko, Vladimir, Summers, Yvonne, Vynnychenko, Ihor, Lee, Sung Yong, Bryl, Maciej, Zer, Alona, Erman, Mustafa, Timcheva, Constanta, Raja, Rajiv, Naicker, Kirsha, Scheuring, Urban, Walker, Jill, Mann, Helen, Chand, Vikram, Mok, Tony

المصدر: Journal of Thoracic Oncology ; volume 18, issue 1, page 106-119 ; ISSN 1556-0864

الإتاحة: https://doi.org/10.1016/j.jtho.2022.09.223Test
https://api.elsevier.com/content/article/PII:S1556086422018238?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1556086422018238?httpAccept=text/plainTest

المؤلفون: Cheng, Ying, Zhou, Qing, Han, Baohui, Fan, Yun, Shan, Li, Chang, Jianhua, Sun, Si, Fang, Jian, Chen, Yuan, Sun, Jianguo, Wu, Gang, Mann, Helen, Naicker, Kirsha, Shire, Norah, Mok, Tony, de Castro, Gilberto

المصدر: Lung Cancer ; volume 178, page 87-95 ; ISSN 0169-5002

مصطلحات موضوعية: Cancer Research, Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.lungcan.2023.01.013Test
https://api.elsevier.com/content/article/PII:S0169500223000430?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0169500223000430?httpAccept=text/plainTest

المؤلفون: Cunha, Mateus Trinconi, de Souza Borges, Ana Paula, Carvalho Jardim, Vinicius, Fujita, André, de Castro, Gilberto

المساهمون: Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado de São Paulo

المصدر: Cancer Medicine ; volume 12, issue 4, page 5099-5109 ; ISSN 2045-7634 2045-7634

الوصف: Background Patients with advanced non‐small cell lung cancer (NSCLC) are a heterogeneous population with short lifespan. We aimed to develop methods to better differentiate patients whose survival was >90 days. Methods We evaluated 83 characteristics of 106 treatment‐naïve, stage IV NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) >1. Automated machine learning was used to select a model and optimize hyperparameters. 100‐fold bootstrapping was performed for dimensionality reduction for a second (“lite”) model. Performance was measured by C‐statistic and accuracy metrics in an out‐of‐sample validation cohort. The “lite” model was validated on a second independent, prospective cohort ( N = 42). Network analysis (NA) was performed to evaluate the differences in centrality and connectivity of features. Results The selected method was ExtraTrees Classifier, with C‐statistic of 0.82 ( p < 0.01) and accuracy of 0.81 ( p = 0.01). The “lite” model had 16 variables and obtained C‐statistic of 0.84 ( p < 0.01) and accuracy of 0.75 ( p = 0.039) in the first cohort, and C‐statistic of 0.706 ( p < 0.01) and accuracy of 0.714 ( p < 0.01) in the second cohort. The networks of patients with lower survival were more interconnected. Features related to cachexia, inflammation, and quality of life had statistically different prestige scores in NA. Conclusions Machine learning can assist in the prognostic evaluation of advanced NSCLC. The model generated with a reduced number of features showed high accessibility and reasonable metrics. Features related to quality of life, cachexia, and performance status had increased correlation and importance scores, suggesting that they play a role at later disease stages, in line with the biological rationale already described.

الإتاحة: https://doi.org/10.1002/cam4.5254Test

المؤلفون: Fares, Aline F., Martinez, Pedro H., Farina, Pedro H., Bicalho de Souza, Isaac, Araújo, Daniel V., Paiva, Narayana S., Orlando, Ligia F., Colombo, Tatiana Elias, Mascarenhas, Eldsamira, Gelatti, Ana Caroline Z., Baldotto, Clarissa, Zukin, Mauro, Araujo, Luiz Henrique, Mathias, Clarissa, Werutsky, Gustavo, de Castro, Gilberto, Cordeiro de Lima, Vladmir C.

المصدر: JTO Clinical and Research Reports ; volume 3, issue 10, page 100402 ; ISSN 2666-3643

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology

الإتاحة: https://doi.org/10.1016/j.jtocrr.2022.100402Test
https://api.elsevier.com/content/article/PII:S2666364322001266?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666364322001266?httpAccept=text/plainTest

المؤلفون: de Castro, Gilberto, Kudaba, Iveta, Wu, Yi-Long, Lopes, Gilberto, Kowalski, Dariusz M., Turna, Hande Z., Cho, Byoung Chul

الوصف: [No Abstract Available] ; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA ; Medical writing assistance was provided by Kathleen Estes, PhD, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

العلاقة: Journal For Immunotherapy of Cancer; Konferans Öğesi - Uluslararası - Kurum Öğretim Elemanı; https://doi.org/10.1136/jitc-2021-SITC2021.363Test; https://hdl.handle.net/20.500.12831/8255Test; A390; WOS:000774877500352

الإتاحة: https://doi.org/10.1136/jitc-2021-SITC2021.363Test
https://doi.org/20.500.12831/8255Test
https://hdl.handle.net/20.500.12831/8255Test

المؤلفون: Tan, Daniel S.W., Felip, Enriqueta, de Castro, Gilberto, Solomon, Benjamin J., Greystoke, Alastair, Cho, Byoung Chul, Cobo, Manuel, Kim, Tae Min, Ganguly, Sandip, Carcereny, Enric, Paz-Ares, Luis, Bennouna, Jaafar, Garassino, Marina Chiara, Schenker, Michael, Kim, Sang-We, Brase, Jan C., Bury-Maynard, Denise, Passos, Vanessa Q., Deudon, Stéphanie, Dharan, Bharani

المصدر: Journal of Clinical Oncology; 1/10/2024, Vol. 42 Issue 2, p192-204, 15p