Clinical value of early detection of circulating tumour DNA-BRAFV600mut in patients with metastatic melanoma treated with a BRAF inhibitor

Louveau, Baptiste; Tost, Jörg; Mauger, Florence; Sadoux, Aurélie; Podgorniak, Marie-Pierre; How‐Kit, Alexandre; Pagès, Cécile; Roux, J.; Meda, Laetitia Da; Lebbe, Célèste

doi:10.1136/esmoopen-2017-000173

Cited by 8 publications

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“…21 Most of the ctDNA studies in melanoma patients with targeted therapy focused on the detection of progression during therapy and evaluation of progression-free survival (PFS), resulting in a significant shorter PFS in patients with persistent elevated ctDNA values during therapy without declining to zero. 10,11 As all our patients' ctDNA values dropped to zero upon therapy initiation, we cannot check this in our cohort.…”

Section: Discussionmentioning

confidence: 92%

“…Recently, a comprehensive and very detailed review article has been published about the importance of LB in various cancers 6 and several publications report on the high relevance of ctDNA monitoring in metastatic melanoma. [7][8][9][10][11][12][13][14][15] We sought to find out whether BRAF V600 mutant ctDNA can be used to reliably determine progressive disease under targeted therapy and whether patients' prognoses are different if ctDNA is detectable before initiating targeted therapy, ie, at baseline.…”

Section: Introductionmentioning

confidence: 99%

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<p>Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study</p>

Forschner¹,

Weißgraeber²,

Hadaschik³

et al. 2020

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Purpose: BRAF and MEK inhibitors significantly improved the prognosis of metastatic melanoma. Nevertheless, initial treatment response may be only temporary. Liquid biopsies (LB) offer a possibility to monitor patients by measuring circulating tumor DNA (ctDNA). We sought to find out whether ctDNA can be used to reliably determine progressive disease under targeted therapy. In addition, we wanted to check whether ctDNA may represent a possible prognostic marker for survival. Patients and Methods: We included 19 melanoma patients with BRAF and MEK inhibitor therapy. For each patient, a 710 gene panel was analyzed on the latest available tumor tissue before the start of therapy. Repetitive LB were collected in which BRAF V600E/K mutations were monitored using digital droplet PCR (ddPCR). We correlated radiological staging results and overall survival with ctDNA results. Results: In 13 patients, ctDNA was detectable when starting targeted therapy, whereas in six patients, ddPCR was always negative, which we confirmed with ultra-deep sequencing. All patients with initially detectable ctDNA had ctDNA values declining to zero during followup, increasing again at the time of extracerebral progression or even slightly before detection by imaging. Survival was significantly worse for patients with elevated LDH (p=0.034) or detectable ctDNA (p=0.008) at the start of targeted therapy. Conclusion: Therapy monitoring by ctDNA seems to be a reliable method for detecting extracranial progression, even more sensitive and specific than LDH or S100B. However, due to the small number of cases in our study, further studies are necessary.

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Section: Discussionmentioning

confidence: 92%