Targeted therapy in metastaical melanoma: Clinical evaluation and biomarkers for response

Abstract

BRAF-MEK-inhibition and real world data in metastatic melanoma: Clinical evaluation and biomarkers for response Degree project, programme in medicine, 2018 Christoffer Kvarnström Supervisors: Lars Ny and Henrik Jespersen Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden Background: Previous trials has demonstrated efficacy for dabrafenib + trametinib in treating metastatic melanoma. In this setting S100b is often used as biomarker in clinical routine but has not yet been validated for the purpose. Aim: 1) To evaluate the use of the BRAF-MEK-inhibitors dabrafenib and trametinib in patients with metastatic melanoma at a single institution in a clinical setting. 2) To evaluate the use of S100b as a biomarker for treatment response and disease progression in the same population. Method: Retrospective descriptive study of medical records from all patients starting treatment with dabrafenib and trametinib between 1st of February 2016 to 31st of January 2018. Survival analysis and description of S100b concentrations in relation to treatment response and disease progression. Results: 59 patients received dabrafenib and trametinib for the first time. The clinical response rate (CRR) was 83.1%. The overall survival (OS) rate at 12 months was 65.0%. Median OS was 15 months. The progression free survival (PFS) rate at 12 months was 20.6%. Median PFS was 6.5 months. Patients with brain metastases had a significantly lower OS compared to other patients (median 9.3 months compared to 19.9 months). 94.6% of the patients responding to treatment had a concordant decrease in S100b concentration. 50% of the patients not responding to treatment had a decrease in S100b concentration. Approximately 2/3 of all patients that progressed in their disease had an elevated S100b concentration at date of progression (+/- 1 week), or 2-14 weeks before disease progression. In a separate cohort of 12 patients who had previously been treated with a line of BRAF-MEK-inhibitors, 83.3% responded to treatment. Conclusion: Patient treated with dabrafenib + trametinib in this clinical evaluation had a lower OS compared to previous trials. There are however important differences between the treated populations, e.g. in this evaluation, a large subpopulation of patients had brain metastases, which significantly lowered survival. Most patients respond and benefit from treatment but mostly only for a limited amount of time. This is also applicable for patients receiving treatment a second time. The role of S100b as a useful biomarker for predicting