A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma
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A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma. / Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander; Bech, Cecilia; Andersen, Claus Bøgelund; Santoni-Rugiu, Eric.
I: Cancer Chemotherapy and Pharmacology, Bind 70, Nr. 5, 11.2012, s. 743-54.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma
AU - Zimling, Zarah Glad
AU - Sørensen, Jens Benn
AU - Gerds, Thomas Alexander
AU - Bech, Cecilia
AU - Andersen, Claus Bøgelund
AU - Santoni-Rugiu, Eric
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Biomarkers, Tumor/metabolism
KW - Cisplatin/administration & dosage
KW - DNA-Binding Proteins/metabolism
KW - Disease-Free Survival
KW - Drug Resistance, Neoplasm
KW - Endonucleases/metabolism
KW - Female
KW - Humans
KW - Male
KW - Mesothelioma/drug therapy
KW - Middle Aged
KW - Multivariate Analysis
KW - Pleural Neoplasms/drug therapy
KW - Predictive Value of Tests
KW - Prognosis
KW - Survival Rate
KW - Treatment Outcome
KW - Tubulin/metabolism
KW - Vinblastine/administration & dosage
KW - Vinorelbine
U2 - 10.1007/s00280-012-1965-0
DO - 10.1007/s00280-012-1965-0
M3 - Journal article
C2 - 22960937
VL - 70
SP - 743
EP - 754
JO - Cancer Chemotherapy and Pharmacology, Supplement
JF - Cancer Chemotherapy and Pharmacology, Supplement
SN - 0943-9404
IS - 5
ER -
ID: 257672236