Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer
| Autor: | Subbiah, Vivek, Kreitman, Robert J, Wainberg, Zev A, Cho, Jae Yong, Schellens, Jan H M, Soria, Jean Charles, Wen, Patrick Y, Zielinski, Christoph, Cabanillas, Maria E, Urbanowitz, Gladys, Mookerjee, Bijoyesh, Wang, Dazhe, Rangwala, Fatima, Keam, Bhumsuk, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology |
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| Přispěvatelé: | Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research Thyroid Carcinoma Anaplastic 0302 clinical medicine Oximes Antineoplastic Combined Chemotherapy Protocols 80 and over Clinical endpoint Anaplastic Neoplasm Metastasis 6.2 Cellular and gene therapies Fatigue Cancer Aged 80 and over Trametinib education.field_of_study MEK inhibitor Imidazoles Nausea Middle Aged 3. Good health 6.1 Pharmaceuticals 030220 oncology & carcinogenesis Female Patient Safety RAPID COMMUNICATION medicine.drug Proto-Oncogene Proteins B-raf Adult medicine.medical_specialty Fever Adolescent Combination therapy Pyridones Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Population Pyrimidinones Disease-Free Survival Young Adult 03 medical and health sciences Rare Diseases Clinical Research Internal medicine medicine Humans Oncology & Carcinogenesis Anaplastic thyroid cancer education Aged business.industry Thyroid Carcinoma Evaluation of treatments and therapeutic interventions Dabrafenib medicine.disease Regimen 030104 developmental biology Mutation business |
| Zdroj: | Journal of Clinical Oncology, 36(1), 7. American Society of Clinical Oncology Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 36, iss 1 |
| ISSN: | 0732-183X |
| Popis: | Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E–mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E–mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E–mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease. |
| Databáze: | OpenAIRE |
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