1.
Long-term Treatment With Sequential Molecular Targeted Therapy for Xp11.2 Translocation Renal Cell Carcinoma: A Case Report and Review of theĀ Literature.
Kakoki, K, Miyata, Y, Mochizuki, Y, Iwata, T, Obatake, M, Abe, K, Nagayasu, T, Sakai, H
Clinical genitourinary cancer. 2017;(3):e503-e506
2.
Multitargeted Kinase Inhibition in Metastatic Differentiated Radioiodine-Refractory Thyroid Cancer: A Look at New Therapeutic Options for a Rare Disease.
Mischler, K, Kneifel, S, Cathomas, R
Oncology research and treatment. 2016;(9):548-52
Abstract
BACKGROUND Metastatic differentiated thyroid cancer (DTC) is a rare disease that is in the first line treated with iodine-131 radioisotope therapy. Until recently, options were very limited in the case of progressive radioactive-iodine (RAI)-refractory disease. Based on new study results, tyrosine kinase inhibitors (TKIs) have attracted attention. The TKI sorafenib demonstrated significantly improved progression-free survival (PFS) in a phase III trial. Recent data from another phase III trial showed that the TKI lenvatinib achieved high response rates and a large improvement in PFS in metastatic RAI-refractory DTC patients in the first-line setting and after 1 prior line of TKI. However, little is known about the response to lenvatinib in patients pretreated with multiple lines of TKIs. CASE REPORT We present the case of a 45-year-old man with metastatic RAI-refractory DTC progressing after multiple prior treatments with TKIs and chemotherapy. A very good and long-lasting response to lenvatinib was observed. Careful and prospective monitoring as well as management of side effects including dose adaptation were necessary to ensure success of treatment. CONCLUSION Here, we review different novel treatment options for patients with metastatic RAI-refractory DTC.
3.
Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein.
Subbiah, V, Westin, SN, Wang, K, Araujo, D, Wang, WL, Miller, VA, Ross, JS, Stephens, PJ, Palmer, GA, Ali, SM
Journal of hematology & oncology. 2014;:8
Abstract
BACKGROUND Oncologic patients who are extreme responders to molecularly targeted therapy provide an important opportunity to better understand the biologic basis of response and, in turn, inform clinical decision making. Malignant neoplasms with an uncertain histologic and immunohistochemical characterization present challenges both on initial diagnostic workups and then later in management, as current treatment algorithms are based on a morphologic diagnosis. Herein, we report a case of a difficult to characterize sarcoma-like lesion for which genomic profiling with clinical next generation sequencing (NGS) identified the molecular underpinnings of arrested progression(stable disease) under combination targeted therapy within a phase I clinical trial. METHODS Genomic profiling with clinical next generation sequencing was performed on the FoundationOneā¢ platform (Foundation Medicine, Cambridge MA). Histopathology and immunohistochemical studies were performed in the Department of Pathology, MD Anderson Cancer Center (Houston, TX). Treatment was administered in the context of a phase I clinical trial ClinicalTrials.gov Identifier: (NCT01187199). RESULTS The histology of the tumor was that of a spindle cell neoplasm, grade 2 by FNCLCC standards. Immunohistochemical staining was positive for S100 and CD34. Genomic profiling identified the following alterations: a KIAA1549-BRAF gene fusion resulting from a tandem duplication event, a homozygous deletion of PTEN, and frameshift insertion/deletions in CDKN2A A68fs*51, SUFU E283fs*3, and MAP3K1 N325fs*3. The patient had a 25% reduction in tumor (RECIST v1.1) following combination therapy consisting of sorafenib, temsirolimus, and bevazicumab within a phase I clinical trial. CONCLUSIONS The patient responded to combination targeted therapy that fortuitously targeted KIAA1549-BRAF and PTEN loss within a spindle cell neoplasm, as revealed by genomic profiling based on NGS. This is the first report of a tumor driven by a KIAA1549-BRAF fusion responding to sorafenib-based combination therapy.