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
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
- Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial(2021) BROSE, Marcia S.; ROBINSON, Bruce; I, Steven Sherman; KRAJEWSKA, Jolanta; LIN, Chia-Chi; VAISMAN, Fernanda; HOFF, Ana; HITRE, Erika; BOWLES, Daniel W.; HERNANDO, Jorge; FAORO, Leonardo; BANERJEE, Kamalika; OLIVER, Jennifer W.; KEAM, Bhumsuk; CAPDEVILA, JaumeBackground Patients with radioiodine-refractory differentiated thyroid cancer (DTC) previously treated with vascular endothelial growth factor receptor (VEGFR)-targeted therapy have aggressive disease and no available standard of care. The aim of this study was to evaluate the tyrosine kinase inhibitor cabozantinib in this patient population. Methods In this global, randomised, double-blind, placebo-controlled, phase 3 trial, patients aged 16 years and older with radioiodine-refractory DTC (papillary or follicular and their variants) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to oral cabozantinib (60 mg once daily) or matching placebo, stratified by previous lenvatinib treatment and age. The randomisation scheme used stratified permuted blocks of block size six and an interactive voice-web response system; both patients and investigators were masked to study treatment. Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors. Patients receiving placebo could cross over to open-label cabozantinib on disease progression confirmed by blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (confirmed response per Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) in the first 100 randomly assigned patients (objective response rate intention-to-treat [OITT] population) and progression-free survival (time to earlier of disease progression per RECIST version 1.1 or death) in all patients (intention-to-treat [ITT] population), both assessed by BIRC. This report presents the primary objective response rate analysis and a concurrent preplanned interim progression-free survival analysis. The study is registered with ClinicalTrials.gov, NCT03690388, and is no longer enrolling patients. Findings Between Feb 27, 2019, and Aug 18, 2020, 227 patients were assessed for eligibility, of whom 187 were enrolled from 164 clinics in 25 countries and randomly assigned to cabozantinib (n=125) or placebo (n=62). At data cutoff (Aug 19, 2020) for the primary objective response rate and interim progression-free survival analyses, median followup was 6middot2 months (IQR 3middot4-9middot2) for the ITT population and 8middot9 months (7middot1-10middot5) for the OITT population. An objective response in the OITT population was achieved in ten (15%; 99% CI 5middot8-29middot3) of 67 patients in the cabozantinib group versus 0 (0%; 0-14middot8) of 33 in the placebo (p=0middot028) but did not meet the prespecified significance level (alpha=0middot01). At interim analysis, the primary endpoint of progression-free survival was met in the ITT population; cabozantinib showed significant improvement in progression-free survival over placebo: median not reached (96% CI 5middot7-not estimable [NE]) versus 1middot9 months (1middot8-3middot6); hazard ratio 0middot22 (96% CI 0middot13-0middot36; p<0middot0001). Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo, the most frequent of which were palmar-plantar erythrodysaesthesia (13 [10%] vs 0), hypertension (11 [9%] vs 2 [3%]), and fatigue (ten [8%] vs 0). Serious treatment-related adverse events occurred in 20 (16%) of 125 patients in the cabozantinib group and one (2%) of 62 in the placebo group. There were no treatment-related deaths. Interpretation Our results show that cabozantinib significantly prolongs progression-free survival and might provide a new treatment option for patients with radioiodine-refractory DTC who have no available standard of care.
conferenceObject Cabozantinib versus placebo in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who progressed after prior VEGFR-targeted therapy: Outcomes in prespecified subgroups based on histology subtypes.(2022) CAPDEVILA, Jaume; ROBINSON, Bruce; SHERMAN, Steven I.; JARZAB, Barbara; LIN, Chia-Chi; VAISMAN, Fernanda; HOFF, Ana; HITRE, Erika; BOWLES, Daniel W.; WILLIAMSON, Denise; OLIVER, Jennifer Wright; KEAM, Bhumsuk; BROSE, Marcia S.- Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Results from the phase 3 COSMIC-311 trial.(2021) BROSE, Marcia S.; ROBINSON, Bruce; SHERMAN, Steven I.; JARZAB, Barbara; LIN, Chia-Chi; VAISMAN, Fernanda; HOFF, Ana; HITRE, Erika; BOWLES, Daniel W.; FAORO, Leonardo; BANERJEE, Kamalika; OLIVER, Jennifer; KEAM, Bhumsuk; CAPDEVILA, Jaume
conferenceObject Effect of age and lenvatinib treatment on overall survival for patients with I-131-refractory differentiated thyroid cancer in SELECT(2015) BROSE, Marcia S.; SCHLUMBERGER, Martin; TAHARA, Makoto; WIRTH, Lori J.; ROBINSON, Bruce; ELISEI, Rossella; NEWBOLD, Kate; KIYOTA, Naomi; HOFF, Ana O.; DUTCUS, Corina; SONG, James; SHERMAN, Steven I.; TAYLOR, Matthew Hiram- 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.
conferenceObject Cabozantinib (C) versus placebo (P) in patients (pts) with radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC) who have progressed after prior VEGFR-targeted therapy: Outcomes in prespecified subgroups based on prior VEGFR-targeted therapy.(2022) HERNANDO, Jorge; CAPDEVILA, Jaume; ROBINSON, Bruce; SHERMAN, Steven I.; JARZAB, Barbara; LIN, Chia-Chi; VAISMAN, Fernanda; HOFF, Ana; HITRE, Erika; BOWLES, Daniel W.; SEN, Suvajit; OLIVER, Jennifer Wright; KEAM, Bhumsuk; BROSE, Marcia S.- 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 EFFICACY AND SAFETY OF LENVATINIB FOR THE TREATMENT OF PATIENTS WITH I-131-REFRACTORY DIFFERENTIATED THYROID CANCER WITH AND WITHOUT PRIOR VEGF-TARGETED THERAPY(2015) NEWBOLD, Kate; ELISEI, Rosella; TAYLOR, Matthew Hiram; KRZYZANOWSKA, Monika; SHAH, Manisha H.; HOFF, Ana O.; ROBINSON, Bruce; DUTCUS, Corina; SONG, James; HUGHES, Brett; HABRA, Mouhammed AmirconferenceObject Efficacy and safety of lenvatinib for the treatment of patients with I-131-refractory differentiated thyroid cancer with and without prior VEGF-targeted therapy.(2015) NEWBOLD, Kate; ELISEI, Rossella; TAYLOR, Matthew Hiram; KRZYZANOWSKA, Monika K.; SHAH, Manisha H.; HOFF, Ana O.; ROBINSON, Bruce; DUTCUS, Corina; SONG, James; HABRA, Mouhammed AmirconferenceObject A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with I-134-refractory differentiated thyroid cancer (SELECT)(2014) SCHLUMBERGER, Martin; TAHARA, Makoto; WIRTH, Lori J.; ROBINSON, Bruce; BROSE, Marcia S.; ELLSEL, Rossella; DUTCUS, Corina E.; HARES, Begona de las; ZHU, Junming; HABRA, Mouhamed Amir; NEWBOLD, Kate; SHAH, Manisha H.; HOFF, Ana O.; GIANOUKAKIS, Andrew G.; KIYOTA, Naomi; TAYLOR, Matthew Hiram; KIM, Sung-Bae; KRZYRANOWSKA, Monika K.; SHERMAN, Steven I.