byl719 and binimetinib

This was a cohort study on genetic alterations in patients with BRAF. In total, 37 patients were included in this cohort. Genetic alterations in EGFR and in PIK3CA are associated with non-response. A greater fraction of non-responders (75%) versus responders (46%) had at least one genetic alteration in other genes than TP53, APC or BRAF. Secondary resistance mutations (n = 16 patients) were observed most frequently in the PI3K pathway (n = 6) and in receptor tyrosine kinases (n = 4), leading to increased upstream signalling.. Genetic alterations in the PI3K and upstream receptor tyrosine kinases were mostly associated with intrinsic and acquired resistance. By understanding these alterations, simultaneous or alternating treatments with targeted inhibitors might improve response duration.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Biomarkers, Tumor; Carbamates; Cetuximab; Cohort Studies; Colorectal Neoplasms; DNA Mutational Analysis; Drug Resistance, Neoplasm; Female; Humans; Male; Middle Aged; Mutation; Proto-Oncogene Proteins B-raf; Retrospective Studies; Sulfonamides; Thiazoles

MEK inhibitor chemotherapy, used in various malignancies, has been reported to be associated with serous retinal detachments. This study reports serial multimodal imaging focused primarily on infrared reflectance and spectral-domain optical coherence tomography (SD-OCT) in the monitoring of MEK inhibitor retinal toxicity. The benefit of OCT angiography in understanding the pathophysiology of MEK inhibitor toxicity is also shown.

Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Female; Fluorescein Angiography; Follow-Up Studies; Humans; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Middle Aged; Multimodal Imaging; Optical Imaging; Ovarian Neoplasms; Phosphoinositide-3 Kinase Inhibitors; Retina; Retinal Detachment; Thiazoles; Tomography, Optical Coherence