crizotinib and Fibrosarcoma

Heterogeneity in the acquired genetic cause of osimertinib resistance leads to difficulties in understanding and addressing molecular mechanisms of resistance in clinical practice. Recent studies and clinical cases established that altered BRAF could drive osimertinib resistance in an EGFR-independent manner. Herein, we present a case in which an EGFR-positive, MET-amplified nonsmall cell lung cancer (NSCLC) patient acquired BRAF p.D594N mutation on third-line osimertinib plus crizotinib and responded to seventh-line treatment with osimertinib plus MEK inhibitor trametinib. Disease control was maintained for 6 months. BRAF p.D594N is a kinase impaired mutation but leads to increased MEK/ERK signaling, which could activate the downstream signaling of EGFR and induce drug resistance. There has been preclinical evidence supporting dual inhibition of MEK and EGFR for overcoming this resistance. To the best of our knowledge, our case is the first to provide clinical evidence that trametinib plus osimertinib was effective for EGFR-mutant NSCLC patients with acquired BRAF p.D594N mutation. More supporting data and systematic validation studies are needed for comprehensive understanding of this therapy strategy and future applications.

Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Crizotinib; Drug Resistance, Neoplasm; ErbB Receptors; Fibrosarcoma; Humans; Indoles; Lung Neoplasms; Mitogen-Activated Protein Kinase Kinases; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidines; Pyrimidinones

Infantile fibrosarcoma (IFS) is a rare soft-tissue sarcoma, which classically presents as an aggressive and rapidly enlarging tumor over the distal extremities of children in their first year of life. The presence of

Topics: Child, Preschool; Crizotinib; Female; Fibrosarcoma; Gene Fusion; Humans; Lamin Type A; Oncogene Proteins, Fusion; Receptor, trkA; Sequence Analysis, RNA; Treatment Outcome

Topics: Antineoplastic Agents; Crizotinib; Fibrosarcoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Fusion; Humans; Infant; Lamin Type A; Lung Neoplasms; Molecular Targeted Therapy; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor, trkA; Reverse Transcriptase Polymerase Chain Reaction; Spinal Neoplasms; Treatment Outcome