BJMO - volume 18, issue 1, february 2024
Y. Van Herck MD, O. Bechter MD, PhD
Systemic treatment for irresectable or metastatic malignant melanoma has transformed over the past decade. For patients harbouring a BRAF V600 mutation, two standard treatment options exist, namely targeted therapy or anti-PD1 based therapy. For all other patients, immune checkpoint blockade based on monoclonal antibodies against anti-PD1 is considered the standard-of-care. Combination therapy with other checkpoint blockers such as anti-CTLA4 or anti-LAG3 are characterised by an improved outcome but are also associated with higher toxicity – which in case of the anti-PD1/anti-CTLA4 combination can be considerable. Up to date, patient selection for either monotherapy or combination therapy is largely based on patients’ demographics. Recent data suggest that treatment naïve patients with a BRAF V600 mutation have a better outcome when combination therapy with anti-CTLA4/anti-PD1 is given in first-line and BRAF/MEK inhibitory therapy is postponed to second-line. Patients who have exhausted their standard-of-care options should be included in a clinical trial and most scientific activity is evolving in the field of the immunotherapy refractory setting. A staggering number of different targets engaged in increasingly diverse subpopulations of immune effector- and regulator cells including the tumoral and stromal compartment are being explored in both the pre-clinical and clinical setting. These efforts will undoubtedly pave the way for the next transformation in the treatment of patients with malignant melanoma.
(BELG J MED ONCOL 2024;18(1):10–16)
Read moreBJMO - volume 13, issue 7, november 2019
Y. Van Herck MD, O. Bechter MD, PhD
Due to the development of genome-directed therapy and standardised methods of molecular analysis, molecular diagnostics has become an important part of daily practice in clinical oncology, especially in diseases like malignant melanoma where molecular testing has therapeutic implications. Melanoma has one of the highest mutation frequency of all cancers analysed in the TGCA (The Cancer Genome Atlas) and is characterised by an enormous genetic heterogeneity.1 The discovery of ‘driver mutations’ directly involved in melanomagenesis has led to the development of small-molecule kinase inhibitors. The emergence of BRAF and MEK inhibitors has completely changed treatment paradigm for BRAF-mutant metastatic melanoma with dramatically improvement of therapeutic outcomes. Despite high response rates, the duration of response remains limited, mainly due to the development of acquired treatment resistance. In this review the authors try to outline the importance of molecular oncology for malignant melanoma by giving an overview of the most frequent and potentially clinically relevant molecular alterations, the targeted therapies already used in clinical routine and by discussing the problem of acquired resistance and treatment strategies being developed to circumvent these obstacles.
(BELG J MED ONCOL 2019;13(7):277–85)
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