Τίτλος:
Combining BRAF/MEK Inhibitors with Immunotherapy in the Treatment of Metastatic Melanoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The management and prognosis of BRAF-mutant metastatic melanoma have changed drastically following the introduction of immune checkpoint inhibitors and molecularly targeted agents. These treatment options present different mechanisms of action and toxicities but also totally distinct kinetics of their response, including a “relatively” short-lasting benefit in subsets of patients treated with BRAF/MEK inhibitors and a lower response rate in patients treated with immune checkpoint inhibitors. BRAF/MEK inhibitors, when administered prior to or concurrently with immune checkpoint inhibitors, at least transiently alter some immunosuppressive parameters of the tumor microenvironment and theoretically improve sensitivity to immunotherapy. Preclinical data from mouse models with oncogene-addicted melanoma confirmed this beneficial immune/targeted synergy and supported the clinical testing of combinations of BRAF/MEK inhibitors and immune checkpoint inhibitors to improve the activity of upfront anti-melanoma therapies. The first positive phase III results were published in 2020, and triggered the discussion about the benefits, the limitations, as well as the possible implications of combining or sequencing targeted therapies with immune checkpoint inhibitors in everyday practice. Beginning from the interplay of immune/targeted agents within the melanoma microenvironment, this review outlines available information from the retrospective experience up to the late-stage randomized evidence on combinatorial treatments. Many clinical trials are currently underway exploring open questions about optimal timing, new immune biomarkers, and eligible patient subsets for these immune/targeted regimens. Awaiting these results, decision making in the first-line setting for BRAF-mutant melanoma is still guided by the patients’ characteristics and the biological aspects of melanoma. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.
Συγγραφείς:
Ziogas, D.C.
Konstantinou, F.
Bouros, S.
Theochari, M.
Gogas, H.
Περιοδικό:
American Journal of Clinical Dermatology
Λέξεις-κλειδιά:
B Raf kinase; B Raf kinase inhibitor; immune checkpoint inhibitor; mitogen activated protein kinase kinase inhibitor; tumor marker; antineoplastic agent; B Raf kinase; BRAF protein, human; mitogen activated protein kinase kinase; protein kinase inhibitor, Article; cancer combination chemotherapy; cancer immunotherapy; cancer resistance; drug efficacy; drug tolerability; human; metastatic melanoma; nonhuman; preclinical study; priority journal; tumor microenvironment; clinical decision making; clinical trial (topic); drug effect; genetics; immunology; melanoma; microbiology; molecularly targeted therapy; mutation; pathology; patient selection; pharmacology; procedures; skin tumor; treatment outcome, Antineoplastic Combined Chemotherapy Protocols; Clinical Decision-Making; Clinical Trials as Topic; Humans; Immune Checkpoint Inhibitors; Melanoma; Mitogen-Activated Protein Kinase Kinases; Molecular Targeted Therapy; Mutation; Patient Selection; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Treatment Outcome; Tumor Microenvironment
DOI:
10.1007/s40257-021-00593-9
