ANA AMELIA FIALHO DE OLIVEIRA HOFF
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer(2023) HADOUX, J.; ELISEI, R.; BROSE, M. S.; HOFF, A. O.; ROBINSON, B. G.; GAO, M.; JARZAB, B.; ISAEV, P.; KOPECKOVA, K.; WADSLEY, J.; FUEHRER, D.; KEAM, B.; BARDET, S.; SHERMAN, E. J.; TAHARA, M.; HU, M. I.; SINGH, R.; LIN, Y.; SOLDATENKOVA, V; WRIGHT, J.; LIN, B.; MAEDA, P.; CAPDEVILA, J.; WIRTH, L. J.Background Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear.Methods We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety.Results A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P<0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively.Conclusions Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.)
- Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study(2019) CASTINETTI, Frederic; WAGUESPACK, Steven G.; MACHENS, Andreas; UCHINO, Shinya; HASSE-LAZAR, Kornelia; SANSO, Gabriella; ELSE, Tobias; DVORAKOVA, Sarka; QI, Xiao Ping; ELISEI, Rossella; MAIA, Ana Luisa; GLOD, John; LOURENCO JR., Delmar Muniz; VALDES, Nuria; MATHIESEN, Jes; WOHLLK, Nelson; BANDGAR, Tushar R.; DRUI, Delphine; KORBONITS, Marta; DRUCE, Maralyn R.; BRAIN, Caroline; KURZAWINSKI, Tom; PATOCS, Atila; BUGALHO, Maria Joao; LACROIX, Andre; CARON, Philippe; FAINSTEIN-DAY, Patricia; CHAZOT, Francoise Borson; KLEIN, Marc; LINKS, Thera P.; LETIZIA, Claudio; FUGAZZOLA, Laura; CHABRE, Olivier; CANU, Letizia; COHEN, Regis; TABARIN, Antoine; UROIC, Anita Spehar; MAITER, Dominique; LABOUREAU, Sandrine; MIAN, Caterina; PECZKOWSKA, Mariola; SEBAG, Frederic; BRUE, Thierry; MIREBEAU-PRUNIER, Delphine; LECLERC, Laurence; BAUSCH, Birke; BERDELOU, Amandine; SUKURAI, Akihiro; VLCEK, Petr; KRAJEWSKA, Jolanta; BARONTINI, Marta; VARGAS, Carla Vaz Ferreira; VALERIO, Laura; CEOLIN, Lucieli; AKSHINTALA, Srivandana; HOFF, Ana; GODBALLE, Christian; JARZAB, Barbara; JIMENEZ, Camilo; ENG, Charis; IMAI, Tsuneo; SCHLUMBERGER, Martin; GRUBBS, Elizabeth; DRALLE, Henning; NEUMANN, Hartmut P.; BAUDIN, EricBackground Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. Methods This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. Findings 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0.2; hazard ratio 0.35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0.0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0.0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. Interpretation Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.
conferenceObject Impact of lung metastasis on overall survival (OS) in the phase III SELECT study with lenvatinib (LEN) in patients (pts) with radioiodine refractory differentiated thyroid cancer (RR-DTC)(2019) TAHARA, M.; KIYOTA, N.; HOFF, A. O.; BADIU, C.; OWONIKOKO, T. K.; DUTCUS, C. E.; SUZUKI, T.; REN, M.; MISIR, S.; WIRTH, L. J.- LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naive RET-mutant medullary thyroid cancer(2022) WIRTH, Lori J.; BROSE, Marcia S.; ELISEI, Rossella; CAPDEVILA, Jaume; HOFF, Ana O.; I, Mimi Hu; TAHARA, Makoto; ROBINSON, Bruce; GAO, Ming; XIA, Meng; MAEDA, Patricia; SHERMAN, EricSelpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with RET-mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic RET-mutant MTC. The primary objective is to compare progression-free survival (per RECIST 1.1) by blinded independent central review of patients with progressive, advanced, multikinase inhibitor-naive, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib. Key secondary objectives are to compare other efficacy outcomes (per RECIST 1.1) and tolerability of selpercatinib versus cabozantinib or vandetanib. Plain language summary: Selpercatinib (also known by the brand name Retevmo (R)/Retsevmo (R)) is a new treatment available in multiple countries for people with advanced or metastatic RET-mutant medullary thyroid cancer (MTC). Thyroid cancer starts in your thyroid gland and may spread or metastasize to other parts of the body, including lungs, bones, and occasionally the brain, which means the cancer is likely to be advanced. Advanced thyroid cancer can be driven by a gene in your body, one of which is RET. This is a summary of the LIBRETTO-531 study which compares selpercatinib, which is a strong and selective inhibitor of RET, with two approved drugs, cabozantinib and vandetanib. Patients with advanced or metastatic RET-mutant MTC who have not already received treatment with kinase inhibitors are being enrolled. This trial will evaluate how long people during and after treatment live with the disease without it getting worse. Selpercatinib may affect both healthy cells and tumor cells, which can result in side effects, which will also be evaluated in this study. This study is active and currently recruiting new patients.
- Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer(2015) SCHLUMBERGER, Martin; TAHARA, Makoto; WIRTH, Lori J.; ROBINSON, Bruce; BROSE, Marcia S.; ELISEI, Rossella; HABRA, Mouhammed Amir; NEWBOLD, Kate; SHAH, Manisha H.; HOFF, Ana O.; GIANOUKAKIS, Andrew G.; KIYOTA, Naomi; TAYLOR, Matthew H.; KIM, Sung-Bae; KRZYZANOWSKA, Monika K.; DUTCUS, Corina E.; HERAS, Begona de las; ZHU, Junming; SHERMAN, Steven I.Background Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor a, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131). Methods In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety. Results The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related. Conclusions Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.)
conferenceObject A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with I-refractory differentiated thyroid cancer (SELECT)(2014) SCHLUMBERGER, M.; TAHARA, M.; WIRTH, L.; ROBINSON, B.; BROSE, M.; ELISEI, R.; DUTCUS, C.; HERAS, B. de las; ZHU, J.; HABRA, M.; NEWBOLD, K.; SHAH, M. H.; HOFF, A. O.; GIANOUKAKIS, A. G.; KIYOTA, N.; TAYLOR, M.; KIM, S-B; KRZYZANOWSKA, M.; I, S. ShermanconferenceObject Defining 131I-refractory differentiated thyroid cancer: efficacy and safety of lenvatinib by 131I-refractory criteria in the SELECT trial(2015) KIYOTA, N.; ROBINSON, B.; SHAH, M.; HOFF, A. O.; TAYLOR, M.; LI, D.; DUTCUS, C.; LEE, E. K.; KIM, S. B.; TAHARA, M.- Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer(2021) TAHARA, Makoto; KIYOTA, Naomi; HOFF, Ana O.; BADIU, Corin; OWONIKOKO, Taofeek K.; DUTCUS, Corina E.; SUZUKI, Takuya; REN, Min; WIRTH, Lori J.Background: Lung metastases may worsen overall survival (OS) in patients with radioiodine- refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study). Patients and methods: 392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to openlabel lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated. Results: Lenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions >= 1.0 cm (n = 199), >= 1.5 cm (n = 150), >= 2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57-1.01; P = 0.0549). Median OS for lung metastases of >= 1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47 -0.85; PZ0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of >= 1.0 cm, >= 1.5 cm, >= 2.0 cm and <2.0 cm; median OS was shorter in the >= 2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1-49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of >= 1.0 cm after adjustment for baseline characteristics. Conclusions: Lenvatinib treatment resulted in longer OS in patients with lung metastases of >= 1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of >= 1.0 cm. (C) 2021 The Authors.
- LIBRETTO-531: Selpercatinib in patients with treatment (Tx)-naive RET-mutant medullary thyroid cancer (MTC)(2020) HERNANDO, J.; TARASOVA, V.; HU, M. I.; SHERMAN, E. J.; BROSE, M. S.; ROBINSON, B.; TAHARA, M.; WIRTH, L. J.; SASHEGYI, A.; SOLDATENKOVA, V.; LIN, B. K.; WRIGHT, J.; HOFF, A. O.; LEBOULLEUX, S.; ELISEI, R.; CAPDEVILA, J.
- Randomized phase III study of selpercatinib versus cabozantinib or vandetanib in advanced, kinase inhibitornaive, RET-mutant medullary thyroid cancer(2023) HADOUX, J.; ELISEI, R.; BROSE, M. S.; HOFF, A.; ROBINSON, B.; GAO, M.; JARZAB, B.; ISAEV, P.; KOPECKOVA, K.; WADSLEY, J.; FUHRER, D.; KEAM, B.; SHERMAN, E. J.; TAHARA, M.; HU, M. I.; LIN, Y.; MAEDA, P.; WIRTH, L. J.; CASTILLON, J. Capdevila