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 language | English |
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Book series | Cancer Chemotherapy and Pharmacology |
Volume | 70 |
Issue number | 5 |
Pages (from-to) | 743-54 |
Number of pages | 12 |
ISSN | 0943-9404 |
DOIs | |
Publication status | Published - 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