Future of combination therapy with dabrafenib and trametinib in metastatic melanoma

Expert Opinion on Pharmacotherapy
Yasaman ZiaA Daud

Abstract

Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF(V600) mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy. This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib , and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway. Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.

References

Mar 24, 2004·Cell·Paul T C WanUNKNOWN Cancer Genome Project
Feb 16, 2005·The Journal of Biological Chemistry·Nancy H TranJeffrey A Frost
Nov 18, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M BalchVernon K Sondak
Jun 10, 2010·British Journal of Cancer·K H T ParaisoK S M Smalley
Jul 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eric W JosephNeal Rosen
Jan 20, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aidan G GilmartinSylvie G Laquerre
Jan 20, 2012·The New England Journal of Medicine·Fei SuRichard Marais
Jun 6, 2012·The New England Journal of Medicine·Keith T FlahertyUNKNOWN METRIC Study Group
Oct 2, 2012·The New England Journal of Medicine·Keith T FlahertyJeffrey Weber
Dec 19, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kevin B KimKarl D Lewis
Apr 27, 2013·Journal of Hematology & Oncology·Tiangui HuangDelong Liu
Aug 7, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paolo A AsciertoUwe Trefzer
Nov 5, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Simone M GoldingerUNKNOWN Dermatology Cooperative Oncology Group (DeCOG)
Mar 4, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander M Menzies, Georgina V Long
Jun 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gerald S FalchookRichard F Kefford
Jul 16, 2014·Drug, Healthcare and Patient Safety·Jason J Luke, Patrick A Ott
Sep 30, 2014·The New England Journal of Medicine·James LarkinAntoni Ribas
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertDirk Schadendorf
Nov 21, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A M MenziesA Daud
Jul 4, 2015·Dermatology : International Journal for Clinical and Investigative Dermatology·Mirjam BaiterLucie Heinzerling
Jul 5, 2015·Journal of Translational Medicine·Paolo A AsciertoMichael B Atkins

❮ Previous
Next ❯

Citations

Mar 22, 2016·Expert Opinion on Pharmacotherapy·Amélie Boespflug, Luc Thomas
Oct 23, 2016·Life Sciences·Sofia OliveiraRúben Fernandes
Sep 29, 2020·Frontiers in Oncology·Hongjian LiAiping Tong

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Expert Opinion on Drug Safety
Lesly A DossettJonathan S Zager
Expert Opinion on Biological Therapy
Ramya ThotaJeffrey A Sosman
Expert Review of Anticancer Therapy
Leila Khoja, David Hogg
© 2021 Meta ULC. All rights reserved