A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma

Zarah Glad Zimling, Jens Benn Sørensen, Thomas Alexander Gerds, Cecilia Bech, Claus Bøgelund Andersen, Eric Santoni-Rugiu

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

PURPOSE: Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated with cisplatin-vinorelbine. We further explored the possibility of combining markers into a treatment-response profile to increase the predictive power.

METHODS: Formalin-fixed paraffin-embedded tumor specimens from 54 MPM patients included in a phase II trial were evaluated for ERCC1, BRCA1, and class III β-tubulin by immunohistochemistry (IHC). Immunostaining was quantified by an H-score and dichotomized according to upper quartile values. The ERCC1- and class III β-tubulin-status classified patients as treatment resistant (ERCC1 positive + class III β-tubulin positive) or treatment responsive (ERCC1 negative + class III β-tubulin negative). The remaining marker combinations were considered inconclusive.

RESULTS: Fifty patients had tumor tissue available for IHC. Eleven had a responsive profile, and nine had a resistant profile. Thirty patients had an inconclusive profile. Median progression-free survival (PFS) was 6.7 months in the treatment-resistant group, 15.3 months in the treatment-responsive group, and 8.1 months in the inconclusive group (log-rank p = 0.03). Multivariate analysis revealed that treatment-resistant patients had a decreased PFS and overall survival (OS) compared with the treatment-responsive patients (HR 6.45, CI 95 % [2.02-20.64] p = 0.002 and HR 4.64, CI 95 % [1.56-13.79], p = 0.006, respectively). BRCA1 status was associated with neither PFS nor OS.

CONCLUSION: Combined negative ERCC1 and class III β-tubulin immunostaining is associated with significantly prolonged PFS and OS in MPM patients receiving cisplatin-vinorelbine therapy.

Original languageEnglish
Book seriesCancer Chemotherapy and Pharmacology
Volume70
Issue number5
Pages (from-to)743-54
Number of pages12
ISSN0943-9404
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Biomarkers, Tumor/metabolism
  • Cisplatin/administration & dosage
  • DNA-Binding Proteins/metabolism
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Endonucleases/metabolism
  • Female
  • Humans
  • Male
  • Mesothelioma/drug therapy
  • Middle Aged
  • Multivariate Analysis
  • Pleural Neoplasms/drug therapy
  • Predictive Value of Tests
  • Prognosis
  • Survival Rate
  • Treatment Outcome
  • Tubulin/metabolism
  • Vinblastine/administration & dosage
  • Vinorelbine

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