GILBERTO DE CASTRO JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial(aEuro)(2016) CLEMENT, P. M.; GAULER, T.; MACHIELS, J. P.; HADDAD, R. I.; FAYETTE, J.; LICITRA, L. F.; TAHARA, M.; COHEN, E. E. W.; CUPISSOL, D.; GRAU, J. J.; GUIGAY, J.; CAPONIGRO, F.; CASTRO JR., G. de; VIANA, L. de Souza; KEILHOLZ, U.; CAMPO, J. M. del; CONG, X. J.; EHRNROOTH, E.; VERMORKEN, J. B.In the LUX-Head & Neck 1 study, older age (a parts per thousand yen65 years) did not adversely affect the benefit in patient-reported outcomes and antitumor activity observed with afatinib over methotrexate, which was consistent with findings from the overall population. Safety in older patients was also consistent with the overall population, favoring afatinib in terms of fewer dose reductions and discontinuations.In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged a parts per thousand yen65 and < 65 years. Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged a parts per thousand yen65 years (older) and 73% (239 afatinib; 116 methotrexate) < 65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Advancing age (a parts per thousand yen65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. NCT01345682 (ClinicalTrials.gov).
conferenceObject PROs With Ceritinib Versus Chemotherapy in Patients With Previously Untreated ALK-rearranged Nonsquamous NSCLC (ASCEND-4)(2017) TAN, Daniel Shao-Weng; SORIA, Jean-Charles; CASTRO JR., Gilberto De; WU, Yi Long; PAZ-ARES, Luis; WOLF, Juergen; GEATER, Sarayut; ORLOV, Sergey; CORTINOVIS, Diego; YU, Chong-Jen; HOCHMAIR, Maximilian; CORTOT, Alexis; TSAI, Chun-Ming; MORO-SIBILOT, Denis; CAMPELO, Rosario Garcia; BRANLE, Fabrice; SEN, Paramita; STRUEBBE, Gero; MCCULLOCH, Tracey; CRINO, Lucio- Pembrolizumab (pembro) vs docetaxel (doce) for previously treated, PD-L1-expressing NSCLC: Updated outcomes of KEYNOTE-010(2016) HERBST, R. S.; BAAS, P.; KIM, D-W.; FELIP, E.; PEREZ-GRACIA, J. L.; HAN, J-Y.; MOLINA, J.; KIM, J-H.; ARVIS, C. Dubos; AHN, M-J. A.; MAJEM, M.; FIDLER, M. J.; CASTRO JR., G. De; GARRIDO, M.; SHENTU, Y.; LUBINIECKI, G. M.; GARON, E. B.
conferenceObject Development of Machine Learning Model to Estimate Overall Survival in Patients with Advanced NSCLC and ECOG-PS > 1(2021) CUNHA, M.; BORGES, A. P.; CARVALHO, V.; FUJITA, A.; CASTRO JR., G. D.- Responses to Crizotinib Can Occur in High-Level MET-Amplified Non-Small Cell Lung Cancer Independent of MET Exon 14 Alterations(2017) CAPARICA, Rafael; YEN, Cheng Tzu; COUDRY, Renata; IGNATIUS, Sai-Hong; VARELLA-GARCIA, Marileila; CAMIDGE, D. Ross; CASTRO JR., Gilberto deActivation of the MET proto-oncogene (MET) highly sensitive to MET inhibition has recently been described in NSCLC through two mechanisms: high-level amplification of the MNNG HOS Transforming gene (MET) (usually expressed relative to the chromosome 7 centromere [CEP7] when using fluorescence in situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other or both can represent true oncogenic driver states continues to be explored. Cases of MET inhibitor-sensitive NSCLC harboring exon 14 alterations without coincident amplification have already been described. Here we report two cases of MET inhibitor-sensitive NSCLC harboring high-level MET amplification (MET/CEP7 ratio >= 5) without coincident exon 14 alterations, suggesting that these two methods of MET activation can produce independent MET-addicted states in NSCLC. Molecular profiling designed to capture all cases of potentially MET-addicted NSCLC should address both activation mechanisms.
- Lung cancer in Brazil(2018) ARAUJO, Luiz Henrique; BALDOTTO, Clarissa; CASTRO JR., Gilberto de; KATZ, Artur; FERREIRA, Carlos Gil; MATHIAS, Clarissa; MASCARENHAS, Eldsamira; LOPES, Gilberto de Lima; CARVALHO, Heloisa; TABACOF, Jaques; MARTINEZ-MESA, Jeovany; VIANA, Luciano de Souza; CRUZ, Marcelo de Souza; ZUKIN, Mauro; MARCHI, Pedro De; TERRA, Ricardo Mingarini; RIBEIRO, Ronaldo Albuquerque; LIMA, Vladmir Claudio Cordeiro de; WERUTSKY, Gustavo; BARRIOS, Carlos HenriqueLung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer.
conferenceObject Canakinumab with Standard of Care for Patients with Advanced NSCLC: T-cell Infiltration Analysis in CANOPY-1(2023) TAN, D. S.; FELIP, E.; CASTRO JUNIOR, G. de; SOLOMON, B. J.; GREYSTOKE, A.; CHO, B. C.; COBO, M.; KIM, T. M.; GANGULY, S.; WU, J.; DEMANSE, D.; BUTLER, A. A.; BRASE, J. C.; BOSSEN, C.; JOHNSON, B. E.- Letter to the editor: radiomics analysis for predicting pembrolizumab response in patients with advanced rare(2021) CUNHA, Mateus Trinconi; CARVALHO, Vinicius Jardim; LOUREIRO, Rafael Maffei; BRANTIS-DE-CARVALHO, Carlos Eduardo; CINTRA, Murilo Bicudo; CASTRO JUNIOR, Gilberto deA commentary on the original research article: 'Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers'. Of note, the predictor selection process, the cross-validation method, along with the lack of final testing of the developed model with a separated data set may mask overfitting, overestimating performance metrics.
- The wolf in sheep's clothing: Microtomographic aspects of clinically incipient radiation-related caries(2016) MORAIS-FARIA, Karina; NEVES-SILVA, Rodrigo; LOPES, Marcio-Ajudarte; RIBEIRO, Ana-Carolina-Prado; CASTRO JR., Gilberto de; CONCEICAO-VASCONCELOS, Karina-Gondim-Moutinho da; BRANDAO, Thais-Bianca; SANTOS-SILVA, Alan-RogerBackground: Radiation-related caries (RRC) can cause rapid progression, with a high potential for dental destruction affecting mainly cervical and incisal areas. Unlike the injuries that occur in the conventional caries, incipient RRC present in unusual surfaces have difficult diagnosis and classification stages of cavitation. Material and Methods: Evaluate the radiographic patterns of demineralization of RRC by using micro-CT. Ten teeth with incipient RRC and 10 teeth with incipient conventional caries (control group) matched by anatomic teeth group and caries affected surfaces were evaluated by X-ray microtomography (micro-CT) Skyscan 1174V2 (50Kv, 1.3 megapixel, Kontich, Belgium). Teeth were placed in a standard position for micro-CT (coronal, transaxial and sagittal sections) during images acquisition. Lesions were classified according to the depth of invasion and relationship with enamel, dentin and pulp. Results: RRC samples presented deeper lesions with higher involvement of enamel and dentin. Control group presented focal and superficial lesions with lower involvement of enamel and dentin. Conclusions: Incipient RRC present aggressive microtomographic patterns of demineralization when compared to conventional caries, as indicated by deep lesions, regardless of its clinically incipient aspects.
- First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study(2017) SORIA, Jean-Charles; TAN, Daniel S. W.; CHIARI, Rita; WU, Yi-Long; PAZ-ARES, Luis; WOLF, Juergen; GEATER, Sarayut L.; ORLOV, Sergey; CORTINOVIS, Diego; YU, Chong-Jen; HOCHMAIR, Maximillian; CORTOT, Alexis B.; TSAI, Chun-Ming; MORO-SIBILOT, Denis; CAMPELO, Rosario G.; MCCULLOCH, Tracey; SEN, Paramita; DUGAN, Margaret; PANTANO, Serafino; BRANLE, Fabrice; MASSACESI, Cristian; CASTRO JR., Gilberto deBackground The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients. Methods This randomised, open-label, phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries. Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m(2) or carboplatin AUC 5-6 plus pemetrexed 500 mg/m(2)] every 3 weeks for four cycles followed by maintenance pemetrexed); randomisation was stratified by World Health Organization performance status (0 vs 1-2), previous neoadjuvant or adjuvant chemotherapy, and presence of brain metastases as per investigator's assessment at screening. Investigators and patients were not masked to treatment assignment. The primary endpoint was blinded independent review committee assessed progression-free survival, based on all randomly assigned patients (the full analysis set). Efficacy analyses were done based on the full analysis set. All safety analyses were done based on the safety set, which included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01828099. Findings Between Aug 19, 2013, and May 11, 2015, 376 patients were randomly assigned to ceritinib (n=189) or chemotherapy (n=187). Median progression-free survival (as assessed by blinded independent review committee) was 16.6 months (95% CI 12.6-27.2) in the ceritinib group and 8.1 months (5.8-11.1) in the chemotherapy group (hazard ratio 0.55 [95% CI 0.42-0.73]; p<0.00001). The most common adverse events were diarrhoea (in 160 [85%] of 189 patients), nausea (130 [69%]), vomiting (125 [66%]), and an increase in alanine aminotransferase (114 [60%]) in the ceritinib group and nausea (in 97 [55%] of 175 patients), vomiting (63 [36%]), and anaemia (62 [35%]) in the chemotherapy group. Interpretation First-line ceritinib showed a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC.