Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer

Anne M. Traynor; Joan H. Schiller; Laura P. Stabile; Jill M. Kolesar; Jens C. Eickhoff; Sanja Dacic; Tien Hoang; Sarita Dubey; Sarah M. Marcotte; Jill M. Siegfried

doi:10.1016/j.lungcan.2008.07.002

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Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer

Journal article

Peer reviewed

Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer

Anne M. Traynor, Joan H. Schiller, Laura P. Stabile, Jill M. Kolesar, Jens C. Eickhoff, Sanja Dacic, Tien Hoang, Sarita Dubey, Sarah M. Marcotte and Jill M. Siegfried

Lung cancer (Amsterdam, Netherlands), Vol.64(1), pp.51-59

04/01/2009

DOI: 10.1016/j.lungcan.2008.07.002

PMCID: PMC3164240

PMID: 18701186

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https://www.ncbi.nlm.nih.gov/pmc/articles/3164240View

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Abstract

Estrogen receptor beta (ERβ) has been detected in non-small cell lung cancer (NSCLC) cell lines and tumor specimens. The ER down-regulator, fulvestrant, blocked estradiol-stimulation of tumor growth and gene transcription in NSCLC preclinical models and showed additive effects with the epidermal growth factor receptor (EGFR) inhibitor gefitinib. The safety and tolerability of combination therapy with the EGFR inhibitor, gefitinib, and fulvestrant was explored. Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Twenty-two patients were enrolled. Eight patients had adenocarcinoma, six NSCLC-NOS, four squamous cell, and four BAC. Seven patients were never-smokers. Eight patients received ≥2 lines of prior chemotherapy, six received one prior chemotherapy, and eight were treatment-naïve. One patient experienced grade 4 dyspnea possibly related to treatment; all other grade 3/4 toxicities were unrelated to treatment. Twenty patients were evaluable for response: three partial responses (PRs) were confirmed (response rate of 15%, 95% CI: 5–36%). The median progression-free survival (PFS), overall survival (OS), and estimated 1-year OS were 12 weeks (3–112 weeks), 38.5 weeks (7–135 weeks), and 41% (95% CI: 20–62%), respectively. Survival outcomes did not differ by prior lines of therapy. A subset analysis revealed that OS in the eight patients whose tumors exhibited at least 60% ERβ nuclear IHC staining measured 65.5 weeks, while that of the five patients with ERβ staining of less than 60% was 21 weeks. One patient with bronchioalveolar carcinoma (BAC) and a PR had an EGFR L858R mutation in exon 21. There was no correlation between ERβ IHC expression and histology or smoking history. Combination therapy with gefitinib and fulvestrant in this population was well tolerated and demonstrated disease activity.

Age

Epidermal growth factor receptor

Estrogen receptor

Hormonal treatment

Non-small cell lung cancer

Sex

Details

Title: Subtitle: Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer
Creators: Anne M. Traynor - University of Wisconsin Carbone Cancer Center
Joan H. Schiller - The University of Texas Southwestern Medical Center
Laura P. Stabile - University of Pittsburgh
Jill M. Kolesar - University of Wisconsin Carbone Cancer Center
Jens C. Eickhoff - University of Wisconsin Carbone Cancer Center
Sanja Dacic - University of Pittsburgh School of Medicine
Tien Hoang - University of Wisconsin Carbone Cancer Center
Sarita Dubey - University of California, San Francisco
Sarah M. Marcotte - University of Wisconsin Carbone Cancer Center
Jill M. Siegfried - University of Pittsburgh
Resource Type: Journal article
Publication Details: Lung cancer (Amsterdam, Netherlands), Vol.64(1), pp.51-59
DOI: 10.1016/j.lungcan.2008.07.002
PMID: 18701186
PMCID: PMC3164240
NLM abbreviation: Lung Cancer
ISSN: 0169-5002
eISSN: 1872-8332
Publisher: Elsevier Ireland Ltd
Language: English
Date published: 04/01/2009
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984696540402771

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