TY - JOUR
T1 - A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant plural 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 b-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 b-Tubulin by immunohistochemistry (IHC). Immunostaining was quantified by an H-score and dichotomized according to upper quartile values. The ERCC1- and class III b-Tubulinstatus classified patients as treatment resistant (ERCC1 positive class III b-Tubulin positive) or treatment responsive (ERCC1 negative class III b-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 treatmentresponsive 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 treatmentresponsive 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 b-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 b-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 b-Tubulin by immunohistochemistry (IHC). Immunostaining was quantified by an H-score and dichotomized according to upper quartile values. The ERCC1- and class III b-Tubulinstatus classified patients as treatment resistant (ERCC1 positive class III b-Tubulin positive) or treatment responsive (ERCC1 negative class III b-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 treatmentresponsive 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 treatmentresponsive 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 b-Tubulin immunostaining is associated with significantly prolonged PFS and OS in MPM patients receiving cisplatin- vinorelbine therapy.
M3 - Journal article
SN - 0344-5704
VL - 70
SP - 743
EP - 754
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 5
ER -