Serum S100B and LDH at Baseline and During Therapy Predict the Outcome of Metastatic Melanoma Patients Treated with BRAF Inhibitors

Target Oncol. 2021 Mar;16(2):197-205. doi: 10.1007/s11523-021-00792-8. Epub 2021 Feb 8.

Abstract

Background: Despite impressive response rates, most patients with advanced melanoma ultimately progress following therapy with B-Raf proto-oncogene (BRAF) inhibitors (BRAFi). Therefore, frequent radiologic assessments are necessary, and reliable serum biomarkers would be beneficial for disease monitoring.

Objective: This study investigated the ability of lactate dehydrogenase (LDH) and S100 calcium-binding protein B (S100B) to detect response and disease progression during treatment with BRAFi.

Patients and methods: Baseline levels of LDH and S100B and repeated measurements during therapy were recorded retrospectively in 191 patients with metastatic melanoma. LDH and S100B levels were compared between distinct time points (baseline, first follow-up visit [FV], best objective response [BR], and progressive disease [PD]). The prognostic ability of the serum biomarkers in relation to disease-specific survival (DSS) was assessed with univariable and multivariable Cox regression analysis.

Results: Elevated baseline LDH and S100B correlated with impaired DSS. In contrast with LDH (P = 0.12), S100B levels at FV correlated with response (P = 0.0030). Both markers significantly decreased during the first weeks of BRAFi treatment (LDH, P = 0.00034; S100B, P < 0.0001) and increased between BR and PD (LDH, P = 0.016; S100B, P < 0.0001). Patients with elevated S100B (P = 0.00062) but not with elevated LDH (P = 0.067) at the time point of radiologically confirmed PD showed significantly impaired DSS after PD. Interestingly, DSS after PD differed significantly according to S100B levels determined as early as 8 weeks (median) before PD (P = 0.0024).

Conclusions: LDH and S100B are suitable serum biomarkers during therapy with BRAFi. S100B shows stronger correlation with response and exhibits more accuracy in predicting PD. Close biomarker monitoring with S100B is recommended during treatment with BRAFi to detect PD early.

MeSH terms

  • Humans
  • L-Lactate Dehydrogenase / blood*
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Retrospective Studies
  • S100 Calcium Binding Protein beta Subunit / metabolism*
  • Treatment Outcome

Substances

  • MAS1 protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Mas
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • L-Lactate Dehydrogenase
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf