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
31 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 31
- 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
- Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Updated results from the phase III COSMIC-311 trial and prespecified subgroup analyses by prior therapy(2021) CAPDEVILA, J.; ROBINSON, B.; SHERMAN, S. I.; JARZAB, B.; LIN, C-C.; VAISMAN, F.; HOFF, A. O.; HITRE, E.; BOWLES, D. W.; SEN, S.; PATEL, P.; OLIVER, J.; KEAM, B.; BROSE, M. S.
- Endocrine side effects of cancer immunotherapy(2017) CUKIER, Priscilla; SANTINI, Fernando C.; SCARANTI, Mariana; HOFF, Ana O.Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L) 1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies.
- 5th International ACC Symposium: Future and Current Therapeutic Trials in Adrenocortical Carcinoma(2016) HOFF, Ana O.; BERRUTI, AlfredoAdrenocortical carcinoma (ACC) is a rare and complex disease associated with a high mortality rate. Despite intensive translational and clinical research, prognosis remains poor. Over the past decade, a significant effort has been made to develop multinational, collaborative studies to better understand the pathogenesis and clinical features of this rare disease in attempt to improve the therapeutic strategies and patient outcome. The results of both standard and newer treatments are discussed in this review as well as the recent discovery of pathways involved in ACC pathogenesis that provide the rationale to introduce new molecular target therapies. Finally, remaining issues regarding how to improve available therapies in adjuvant setting are raised and addressed.
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- Is there a role for diagnostic scans in the management of intermediate-risk thyroid cancer?(2022) DANILOVIC, Debora L. S.; COURA-FILHO, George B.; RECCHIA, Giulianna M.; CASTRONEVES, Luciana A.; MARUI, Suemi; BUCHPIGUEL, Carlos A.; HOFF, Ana O.; KOPP, PeterRadioiodine (RAI) is selectively recommended for intermediate-risk differentiated thyroid carcinomas (DTC). The information gleaned from pretherapy stimulated thyroglobulin levels (sTg) and diagnostic I-131 whole-body scans (DxWBS) to guide therapy remains controversial. The present study aimed at evaluating the impact of preablation sTg and DxWBS in the management of intermediate-risk DTC. A retrospective analysis of 301 intermediate-risk DTC patients submitted to total thyroidectomy and RAI therapy was performed. Pretherapy sTg and DxWBS and post-therapy WBS (RxWBS) findings were analyzed and compared to outcomes. Fifty-two patients (17.3%) had metastases diagnosed by DxWBS and/or RxWBS. The DxWBS identified 10.6% of patients with functioning metastases, including unexpected distant metastases. If combined with SPECT-CT, DxWBS detected RAI-avid metastases more frequently, particularly lymph node metastases (13.1% vs 4.2% planar WBS, P = 0.015). The DxWBS findings modified patient management in 8.3%. A pretherapy sTg <1 ng/mL was associated with a low false-negative rate for the presence of metastases (5.2%), and its performance in excluding metastasis was improved by a negative DxWBS (2.7% of patients with both negative exams had metastases in RxWBS). A sTg <1 ng/mL predicted statistically significant lower rates of recurrent/persistent disease and biochemical/structural incomplete responses. In conclusion, preablation sTg and DxWBS contribute to the detection of unknown or persistent metastatic disease in intermediate-risk DTC patients. A sTg <1 ng/mL in combination with a negative DxWBS is highly suggestive of the absence of remaining malignant disease, and one may consider deferring RAI ablation if both exams are negative. A stunning effect is rarely observed and it does not impair proper treatment of metastases.
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.conferenceObject Effect of Age on the Efficacy and Safety of Cabozantinib compared to Placebo in Patients with radioiodine-refractory (RAIR) differentiated Thyroid Cancer (DTC) who progressed after VEGFR-directed Therapy: Subgroup Analysis of the Phase 3 COSMIC 311 Study(2022) DUQUE-AFONSO, J.; ROBINSON, B.; I, S. Sherman; KRAJEWSKA, J.; LIN, C-C; VAISMAN, F.; HOFF, A. O.; HITRE, E.; BOWLES, D. W.; HERNANDO, J.; BANERJEE, K.; LEVYTSKYY, R. M.; OLIVER, J. W.; KEAM, B.; CAPDEVILA, J.; BROSE, M.