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01.12.2015 | Original article

Epidermal Growth Factor Receptor (EGFR) Pathway Biomarkers in the Randomized Phase III Trial of Erlotinib Versus Observation in Ovarian Cancer Patients with No Evidence of Disease Progression after First-Line Platinum-Based Chemotherapy

verfasst von: Evelyn Despierre, Ignace Vergote, Ryan Anderson, Corneel Coens, Dionyssios Katsaros, Fred R. Hirsch, Bram Boeckx, Marileila Varella-Garcia, Annamaria Ferrero, Isabelle Ray-Coquard, Els M. J. J. Berns, Antonio Casado, Diether Lambrechts, Antonio Jimeno, on behalf of the European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG), Groupe d’Investigateurs Nationaux pour les Etudes des Cancers de l’Ovaire (GINECO), Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (A-AGO), National Cancer Research Institute (NCRI), Australia New Zealand Gynaecological Oncology Group (ANZGOG), and the Mario Negri Gynecologic Oncology group (MaNGO)

Erschienen in: Targeted Oncology | Ausgabe 4/2015

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Abstract

Background

In this work, we aimed to identify molecular epidermal growth factor receptor (EGFR) tissue biomarkers in patients with ovarian cancer who were treated within the phase III randomized European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG) 55041 study comparing erlotinib with observation in patients with no evidence of disease progression after first-line platinum-based chemotherapy.

Methods

Somatic mutations in KRAS, BRAF, NRAS, PIK3CA, EGFR, and PTEN were determined in 318 (38 %) and expression of EGFR, pAkt, pMAPK, E-cadherin and Vimentin, and EGFR and HER2 gene copy numbers in 218 (26 %) of a total of 835 randomized patients. Biomarker data were correlated with progression-free survival (PFS) and overall survival (OS).

Results

Only 28 mutations were observed among KRAS, BRAF, NRAS, PIK3CA, EGFR, and PTEN (in 7.5 % of patients), of which the most frequent were in KRAS and PIK3CA. EGFR mutations occurred in only three patients. When all mutations were pooled, patients with at least one mutation in KRAS, NRAS, BRAF, PIK3CA, or EGFR had longer PFS (33.1 versus 12.3 months; HR 0.57; 95 % CI 0.33 to 0.99; P = 0.042) compared to those with wild-type tumors. EGFR overexpression was detected in 93 of 218 patients (42.7 %), and 66 of 180 patients (36.7 %) had EGFR gene amplification or high levels of copy number gain. Fifty-eight of 128 patients had positive pMAPK expression (45.3 %), which was associated with inferior OS (38.9 versus 67.0 months; HR 1.81; 95 % CI 1.11 to 2.97; P = 0.016). Patients with positive EGFR fluorescence in situ hybridization (FISH) status had worse OS (46.1 months) than those with negative status (67.0 months; HR 1.56; 95 % CI 1.01 to 2.40; P = 0.044) and shorter PFS (9.6 versus 16.1 months; HR 1.57; 95 % CI 1.11 to 2.22; P = 0.010). None of the investigated biomarkers correlated with responsiveness to erlotinib.

Conclusions

In this phase III study, increased EGFR gene copy number was associated with worse OS and PFS in patients with ovarian cancer. It remains to be determined whether this association is purely prognostic or is also predictive.

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Titel: Epidermal Growth Factor Receptor (EGFR) Pathway Biomarkers in the Randomized Phase III Trial of Erlotinib Versus Observation in Ovarian Cancer Patients with No Evidence of Disease Progression after First-Line Platinum-Based Chemotherapy
verfasst von: Evelyn Despierre
Ignace Vergote
Ryan Anderson
Corneel Coens
Dionyssios Katsaros
Fred R. Hirsch
Bram Boeckx
Marileila Varella-Garcia
Annamaria Ferrero
Isabelle Ray-Coquard
Els M. J. J. Berns
Antonio Casado
Diether Lambrechts
Antonio Jimeno
on behalf of the European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG), Groupe d’Investigateurs Nationaux pour les Etudes des Cancers de l’Ovaire (GINECO), Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (A-AGO), National Cancer Research Institute (NCRI), Australia New Zealand Gynaecological Oncology Group (ANZGOG), and the Mario Negri Gynecologic Oncology group (MaNGO)
Publikationsdatum: 01.12.2015
Verlag: Springer International Publishing
Erschienen in: Targeted Oncology / Ausgabe 4/2015
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-015-0369-6

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Epidermal Growth Factor Receptor (EGFR) Pathway Biomarkers in the Randomized Phase III Trial of Erlotinib Versus Observation in Ovarian Cancer Patients with No Evidence of Disease Progression after First-Line Platinum-Based Chemotherapy