1Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Stem Cell Transplantation, Beckman Research Institute, City of Hope, CA, 91010, USA
2High Throughput Screening Core, Department of Share Resources, Beckman Research Institute, City of Hope, Duarte, CA, 91010, USA
3Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, 91010, USA
*Corresponding author: Yan Xing, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, 91010, USA
Submission: March 15, 2022 Published: April 08, 2022
The landscape of advanced melanoma therapies has undergone a dramatic transformation over the last decade. The better characterization of the Mitogen-Activated Protein Kinase (MAPK) pathway led to the development of BRAF and MEK inhibitors (BRAFi and MEKi), such as vemurafenib and trametinib, which have shown substantial improvement in patient response and survival rate. To further address the rapid resistance developed following BRAFi monotherapy, combined BRAFi and MEKi doublets were developed and have represented the standard of care for targeted therapy of advanced melanoma patients. The deeper understanding of immune cells and their interactions with tumor cells prompted the development of Immune Checkpoint Inhibitors (ICIs) such as ipilimumab and nivolumab, which have shown tremendous clinical benefit and led to the emergence of BRAFi+MEKi+ICI triplet treatment. In this article, we review the evolvement of treatment approaches for advanced BRAF V600 mutant melanoma and discuss the unmet needs and challenges to be addressed by future studies.
Keywords: Advanced melanoma; BRAF V600 mutation; Targeted therapy; Immunotherapy; Triplet therapy; Sequence of systemic therapies; Clinical trials
Abbreviations: MAPK: Mitogen-Activated Protein Kinase; FDA: Food and Drug Administration; CTLA-4: Cytotoxic T lymphocyte Antigen-4; PD-1: Programmed Cell Death Protein-1; OS: Overall Survival; PFS: Progression Free Survival; ORR: Objective Response Rate; CRR: Complete Response Rate; DOR: Duration of Response; LAG-3: Lymphocyte-Activation Gene-3; GM-CSF: Granulocyte Macrophage Colony-Stimulating Factor; T-VEC: Talimogene Laherparepvec, ICI: Immune Checkpoint Inhibitors