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

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

Introduction: 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. Methods: Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Results: 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. Conclusions: Combination therapy with gefitinib and fulvestrant in this population was well tolerated and demonstrated disease activity.

Original language	English (US)
Pages (from-to)	51-59
Number of pages	9
Journal	Lung Cancer
Volume	64
Issue number	1
DOIs	https://doi.org/10.1016/j.lungcan.2008.07.002
State	Published - Apr 2009

Bibliographical note

Funding Information:
This trial was supported by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716, the University of Pittsburgh Cancer Institute Lung Cancer SPORE (P50 CA9045440), and the AstraZeneca Corporation. The AstraZeneca Corporation exerted no role in the design of this study, in the data collection, analyses and interpretation of data, nor in the writing of this manuscript.

Keywords

Age
Epidermal growth factor receptor
Estrogen receptor
Hormonal treatment
Non-small cell lung cancer
Sex

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.lungcan.2008.07.002

OpenUrl availability

Full text

Cite this

@article{69c1979f887540f497f0b5b52c93f030,

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

abstract = "Introduction: 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. Methods: Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Results: 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-na{\"i}ve. 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. Conclusions: Combination therapy with gefitinib and fulvestrant in this population was well tolerated and demonstrated disease activity.",

keywords = "Age, Epidermal growth factor receptor, Estrogen receptor, Hormonal treatment, Non-small cell lung cancer, Sex",

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

note = "Funding Information: This trial was supported by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716, the University of Pittsburgh Cancer Institute Lung Cancer SPORE (P50 CA9045440), and the AstraZeneca Corporation. The AstraZeneca Corporation exerted no role in the design of this study, in the data collection, analyses and interpretation of data, nor in the writing of this manuscript.",

year = "2009",

month = apr,

doi = "10.1016/j.lungcan.2008.07.002",

language = "English (US)",

volume = "64",

pages = "51--59",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer

AU - Traynor, Anne M.

AU - Schiller, Joan H.

AU - Stabile, Laura P.

AU - Kolesar, Jill M.

AU - Eickhoff, Jens C.

AU - Dacic, Sanja

AU - Hoang, Tien

AU - Dubey, Sarita

AU - Marcotte, Sarah M.

AU - Siegfried, Jill M.

N1 - Funding Information: This trial was supported by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716, the University of Pittsburgh Cancer Institute Lung Cancer SPORE (P50 CA9045440), and the AstraZeneca Corporation. The AstraZeneca Corporation exerted no role in the design of this study, in the data collection, analyses and interpretation of data, nor in the writing of this manuscript.

PY - 2009/4

Y1 - 2009/4

N2 - Introduction: 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. Methods: Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Results: 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. Conclusions: Combination therapy with gefitinib and fulvestrant in this population was well tolerated and demonstrated disease activity.

AB - Introduction: 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. Methods: Post-menopausal women with advanced NSCLC received gefitinib 250 mg po daily and fulvestrant 250 mg IM monthly. Results: 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. Conclusions: Combination therapy with gefitinib and fulvestrant in this population was well tolerated and demonstrated disease activity.

KW - Age

KW - Epidermal growth factor receptor

KW - Estrogen receptor

KW - Hormonal treatment

KW - Non-small cell lung cancer

KW - Sex

UR - http://www.scopus.com/inward/record.url?scp=61449089509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61449089509&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2008.07.002

DO - 10.1016/j.lungcan.2008.07.002

M3 - Article

C2 - 18701186

AN - SCOPUS:61449089509

SN - 0169-5002

VL - 64

SP - 51

EP - 59

JO - Lung Cancer

JF - Lung Cancer

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this