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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalLung Cancer
Volume64
Issue number1
DOIs
StatePublished - Apr 2009

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Non-Small Cell Lung Carcinoma
Estrogen Receptor beta
Epidermal Growth Factor Receptor
Therapeutics
Survival
Staining and Labeling
Carcinoma
gefitinib
fulvestrant
Drug Therapy
Tumor Cell Line
Dyspnea
Disease-Free Survival
Estradiol
Exons
Neoplasms
Histology
Adenocarcinoma
Smoking
History

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Traynor, A. M., Schiller, J. H., Stabile, L. P., Kolesar, J. M., Eickhoff, J. C., Dacic, S., ... Siegfried, J. M. (2009). Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer. Lung Cancer, 64(1), 51-59. https://doi.org/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. / Traynor, Anne M.; Schiller, Joan H.; Stabile, Laura P.; Kolesar, Jill M.; Eickhoff, Jens C.; Dacic, Sanja; Hoang, Tien; Dubey, Sarita; Marcotte, Sarah M.; Siegfried, Jill M.

In: Lung Cancer, Vol. 64, No. 1, 04.2009, p. 51-59.

Research output: Contribution to journalArticle

Traynor, AM, Schiller, JH, Stabile, LP, Kolesar, JM, Eickhoff, JC, Dacic, S, Hoang, T, Dubey, S, Marcotte, SM & Siegfried, JM 2009, 'Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer', Lung Cancer, vol. 64, no. 1, pp. 51-59. https://doi.org/10.1016/j.lungcan.2008.07.002
Traynor, Anne M. ; Schiller, Joan H. ; Stabile, Laura P. ; Kolesar, Jill M. ; Eickhoff, Jens C. ; Dacic, Sanja ; Hoang, Tien ; Dubey, Sarita ; Marcotte, Sarah M. ; Siegfried, Jill M. / Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer. In: Lung Cancer. 2009 ; Vol. 64, No. 1. pp. 51-59.
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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.",
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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.

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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.

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