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

Overview

Journal Target Oncol

Specialty Oncology

Date 2015 May 26

PMID 26004768

Citations 13

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities.

Garlisi B, Lauks S, Aitken C, Ogilvie L, Lockington C, Petrik D Curr Oncol. 2024; 31(7):3826-3844.

PMID: 39057155 PMC: 11275383. DOI: 10.3390/curroncol31070283.

Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer.

Wu J, Li X, Liu H, Liu Y, Liu X Biomed Rep. 2023; 19(6):104.

PMID: 38025833 PMC: 10646763. DOI: 10.3892/br.2023.1686.

Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial.

Forlani L, De Cecco L, Simeon V, Paolini B, Bagnoli M, Cecere S J Exp Clin Cancer Res. 2023; 42(1):83.

PMID: 37041632 PMC: 10088260. DOI: 10.1186/s13046-023-02651-y.

Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.

Wei Y, Erfani S, Schweer D, de Gouvea R, Qadir J, Shi J Mol Ther Oncolytics. 2023; 28:293-306.

PMID: 36911068 PMC: 9999170. DOI: 10.1016/j.omto.2023.02.006.

Targeting Tyrosine Kinases in Ovarian Cancer: Small Molecule Inhibitor and Monoclonal Antibody, Where Are We Now?.

Rendell A, Thomas-Bland I, McCuish L, Taylor C, Binju M, Yu Y Biomedicines. 2022; 10(9).

PMID: 36140214 PMC: 9495728. DOI: 10.3390/biomedicines10092113.

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