1.Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial.
Planchard D1, Kim TM2, Mazieres J3, Quoix E4, Riely G5, Barlesi F6, Souquet PJ7, Smit EF8, Groen HJ9, Kelly RJ10, Cho BC11, Socinski MA12, Pandite L13, Nase C14, Ma B15, D'Amelio A Jr16, Mookerjee B17, Curtis CM Jr18, Johnson BE19. Lancet Oncol. 2016 Apr 11. pii: S1470-2045(16)00077-2. doi: 10.1016/S1470-2045(16)00077-2. [Epub ahead of print]
BACKGROUND: Activating BRAFV600E (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAFV600E mutation.
2.Simultaneous quantification of dabrafenib and trametinib in human plasma using high-performance liquid chromatography-tandem mass spectrometry.
Nijenhuis CM1, Haverkate H2, Rosing H2, Schellens JH3, Beijnen JH4. J Pharm Biomed Anal. 2016 Mar 25;125:270-279. doi: 10.1016/j.jpba.2016.03.049. [Epub ahead of print]
Dabrafenib (Tafinlar®) and trametinib (Mekinist®) are registered for the treatment of patients with BRAF V600 mutation positive unresectable or metastatic melanoma. To support therapeutic drug monitoring (TDM) and clinical pharmacological trials, an assay to simultaneously quantify dabrafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected on an outpatient base and stored at nominally -20°C. Analytes and internal standards (stable isotope labeled compounds) were extracted with TBME. After snap freezing the samples in a dry ice-ethanol bath, the organic layer was transferred to a clean tube and evaporated under a gentle stream of nitrogen gas. The dry extract was then reconstituted with 100μL acetonitrile and 5μL of the final extract was injected and separated on a C18 column with gradient elution, and analyzed with triple quadrupole mass spectrometry in positive-ion mode.
3.Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial.
Chen G1, McQuade JL2, Panka DJ3, Hudgens CW4, Amin-Mansour A5, Mu XJ5, Bahl S5, Jané-Valbuena J5, Wani KM4, Reuben A6, Creasy CA1, Jiang H6, Cooper ZA6, Roszik J1, Bassett RL Jr7, Joon AY7, Simpson LM1, Mouton RD1, Glitza IC1, Patel SP1, Hwu WJ1, Amaria R JAMA Oncol. 2016 Apr 28. doi: 10.1001/jamaoncol.2016.0509. [Epub ahead of print]
Importance: Combined treatment with dabrafenib and trametinib (CombiDT) achieves clinical responses in only about 15% of patients with BRAF inhibitor (BRAFi)-refractory metastatic melanoma in contrast to the higher response rate observed in BRAFi-naïve patients. Identifying correlates of response and mechanisms of resistance in this population will facilitate clinical management and rational therapeutic development.
4.The relative clinical efficacy of trametinib-dabrafenib and cobimetinib-vemurafenib in advanced melanoma: an indirect comparison.
Galván-Banqueri M1, Ubago-Pérez R1, Molina-López T1. J Clin Pharm Ther. 2016 Apr 15. doi: 10.1111/jcpt.12390. [Epub ahead of print]
WHAT IS KNOWN AND OBJECTIVE: Melanoma causes the majority of skin cancer-related deaths. The outcome of melanoma depends on its stage at diagnosis. Currently, for patients with advanced melanoma, two MEK inhibitors (trametinib and cobimetinib) have been authorized by the European Medicines Agency. The main objective of this study was to compare the relative efficacy of trametinib-dabrafenib and cobimetinib-vemurafenib in patients with advanced melanoma through adjusted indirect treatment comparisons (ITCs).
