Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 5, pp 743–754

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
Original Article

DOI: 10.1007/s00280-012-1965-0

Cite this article as:
Zimling, Z.G., Sørensen, J.B., Gerds, T.A. et al. Cancer Chemother Pharmacol (2012) 70: 743. doi:10.1007/s00280-012-1965-0

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.

Keywords

Predictive biomarkerMalignant mesotheliomaERCC1Class III β-tubulinBRCA1

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Zarah Glad Zimling
    • 1
    • 2
  • Jens Benn Sørensen
    • 1
  • Thomas Alexander Gerds
    • 3
  • Cecilia Bech
    • 1
  • Claus Bøgelund Andersen
    • 2
  • Eric Santoni-Rugiu
    • 2
  1. 1.Department of OncologyNational University Hospital of Copenhagen, RigshospitaletCopenhagenDenmark
  2. 2.Department of Pathology5444 National University Hospital of Copenhagen, RigshospitaletCopenhagen EastDenmark
  3. 3.Department of BiostatisticsUniversity of CopenhagenCopenhagenDenmark