Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer

Edward B. Garon; Jill M. Siegfried; Laura P. Stabile; Patricia A. Young; Diana C. Marquez-Garban; David J. Park; Ravi Patel; Eddie H. Hu; Saeed Sadeghi; Rupesh J. Parikh; Karen L. Reckamp; Brad Adams; Robert M. Elashoff; David Elashoff; Tristan Grogan; He Jing Wang; Sanja Dacic; Meghan Brennan; Yacgley Valdes; Simon Davenport; Steven M. Dubinett; Michael F. Press; Dennis J. Slamon; Richard J. Pietras

doi:10.1016/j.lungcan.2018.06.013

Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer

Edward B. Garon, Jill M. Siegfried, Laura P. Stabile, Patricia A. Young, Diana C. Marquez-Garban, David J. Park, Ravi Patel, Eddie H. Hu, Saeed Sadeghi, Rupesh J. Parikh, Karen L. Reckamp, Brad Adams, Robert M. Elashoff, David Elashoff, Tristan Grogan, He Jing Wang, Sanja Dacic, Meghan Brennan, Yacgley Valdes, Simon DavenportSteven M. Dubinett, Michael F. Press, Dennis J. Slamon, Richard J. Pietras

Pharmacology

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

31 Scopus citations

Abstract

Objectives: This open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients. Materials and Methods: Patients with advanced or metastatic NSCLC, ECOG 0–2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150 mg oral daily plus 500 mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150 mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: Among 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (p = 0.77). PFS median 3.5 versus 1.9 months [HR = 0.86, 95% CI (0.52–1.43), p = 0.29] and OS median 9.5 versus 5.8 months [HR = 0.92, 95% CI (0.57–1.48), p = 0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (n = 51), but not EGFR mutant patients (n = 17), median PFS was 3.5 versus 1.7 months [HR = 0.35, 95% CI (0.14-0.86), p = 0.02] and OS was 6.2 versus 5.2 months [HR = 0.72, 95% CI (0.35–1.48), p = 0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (p = 0.03). Treatment was well tolerated with predominant grade 1–2 dermatologic and gastrointestinal adverse effects. Conclusion: Addition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.

Original language	English (US)
Pages (from-to)	91-98
Number of pages	8
Journal	Lung Cancer
Volume	123
DOIs	https://doi.org/10.1016/j.lungcan.2018.06.013
State	Published - Sep 2018

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health grant numbers K23CA149079, P50 CA090440, SPORE CDA FDP-NIHCA090388, NIH CTSIUL1 TR 000124, One Ball Matt Memorial Golf Tournament, V Foundation for Cancer Research, UCLA Jonsson Comprehensive Cancer Center, Wolfen Family Lung Cancer Research Program, Stiles Program in Oncology, Hickey Foundation, National Lung Cancer Partnership, Genentech, AstraZeneca, and F. Hoffmann-La Roche Ltd. This project used the University of Pittsburgh Small Molecule Biomarker Core for analysis of estradiol and estrone.

Funding Information:
This work was supported by the National Institutes of Health grant numbers K23CA149079 , P50 CA090440 , SPORE CDA FDP-NIH CA090388 , NIH CTSI UL1 TR 000124 , One Ball Matt Memorial Golf Tournament , V Foundation for Cancer Research , UCLA Jonsson Comprehensive Cancer Center , Wolfen Family Lung Cancer Research Program , Stiles Program in Oncology, Hickey Foundation , National Lung Cancer Partnership, Genentech, AstraZeneca , and F. Hoffmann-La Roche Ltd . This project used the University of Pittsburgh Small Molecule Biomarker Core for analysis of estradiol and estrone.

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

EGFR
Erlotinib
Estrogen
Estrogen receptor
Fulvestrant
Lung cancer

UN SDGs

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

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10.1016/j.lungcan.2018.06.013

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118115

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Garon, E. B., Siegfried, J. M., Stabile, L. P., Young, P. A., Marquez-Garban, D. C., Park, D. J., Patel, R., Hu, E. H., Sadeghi, S., Parikh, R. J., Reckamp, K. L., Adams, B., Elashoff, R. M., Elashoff, D., Grogan, T., Wang, H. J., Dacic, S., Brennan, M., Valdes, Y., ... Pietras, R. J. (2018). Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer. Lung Cancer, 123, 91-98. https://doi.org/10.1016/j.lungcan.2018.06.013

Garon, EB, Siegfried, JM, Stabile, LP, Young, PA, Marquez-Garban, DC, Park, DJ, Patel, R, Hu, EH, Sadeghi, S, Parikh, RJ, Reckamp, KL, Adams, B, Elashoff, RM, Elashoff, D, Grogan, T, Wang, HJ, Dacic, S, Brennan, M, Valdes, Y, Davenport, S, Dubinett, SM, Press, MF, Slamon, DJ & Pietras, RJ 2018, 'Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer', Lung Cancer, vol. 123, pp. 91-98. https://doi.org/10.1016/j.lungcan.2018.06.013

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title = "Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer",

abstract = "Objectives: This open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients. Materials and Methods: Patients with advanced or metastatic NSCLC, ECOG 0–2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150 mg oral daily plus 500 mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150 mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: Among 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (p = 0.77). PFS median 3.5 versus 1.9 months [HR = 0.86, 95% CI (0.52–1.43), p = 0.29] and OS median 9.5 versus 5.8 months [HR = 0.92, 95% CI (0.57–1.48), p = 0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (n = 51), but not EGFR mutant patients (n = 17), median PFS was 3.5 versus 1.7 months [HR = 0.35, 95% CI (0.14-0.86), p = 0.02] and OS was 6.2 versus 5.2 months [HR = 0.72, 95% CI (0.35–1.48), p = 0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (p = 0.03). Treatment was well tolerated with predominant grade 1–2 dermatologic and gastrointestinal adverse effects. Conclusion: Addition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.",

keywords = "EGFR, Erlotinib, Estrogen, Estrogen receptor, Fulvestrant, Lung cancer",

author = "Garon, {Edward B.} and Siegfried, {Jill M.} and Stabile, {Laura P.} and Young, {Patricia A.} and Marquez-Garban, {Diana C.} and Park, {David J.} and Ravi Patel and Hu, {Eddie H.} and Saeed Sadeghi and Parikh, {Rupesh J.} and Reckamp, {Karen L.} and Brad Adams and Elashoff, {Robert M.} and David Elashoff and Tristan Grogan and Wang, {He Jing} and Sanja Dacic and Meghan Brennan and Yacgley Valdes and Simon Davenport and Dubinett, {Steven M.} and Press, {Michael F.} and Slamon, {Dennis J.} and Pietras, {Richard J.}",

note = "Funding Information: This work was supported by the National Institutes of Health grant numbers K23CA149079, P50 CA090440, SPORE CDA FDP-NIHCA090388, NIH CTSIUL1 TR 000124, One Ball Matt Memorial Golf Tournament, V Foundation for Cancer Research, UCLA Jonsson Comprehensive Cancer Center, Wolfen Family Lung Cancer Research Program, Stiles Program in Oncology, Hickey Foundation, National Lung Cancer Partnership, Genentech, AstraZeneca, and F. Hoffmann-La Roche Ltd. This project used the University of Pittsburgh Small Molecule Biomarker Core for analysis of estradiol and estrone. Funding Information: This work was supported by the National Institutes of Health grant numbers K23CA149079 , P50 CA090440 , SPORE CDA FDP-NIH CA090388 , NIH CTSI UL1 TR 000124 , One Ball Matt Memorial Golf Tournament , V Foundation for Cancer Research , UCLA Jonsson Comprehensive Cancer Center , Wolfen Family Lung Cancer Research Program , Stiles Program in Oncology, Hickey Foundation , National Lung Cancer Partnership, Genentech, AstraZeneca , and F. Hoffmann-La Roche Ltd . This project used the University of Pittsburgh Small Molecule Biomarker Core for analysis of estradiol and estrone. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2018",

month = sep,

doi = "10.1016/j.lungcan.2018.06.013",

language = "English (US)",

volume = "123",

pages = "91--98",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer

AU - Garon, Edward B.

AU - Siegfried, Jill M.

AU - Stabile, Laura P.

AU - Young, Patricia A.

AU - Marquez-Garban, Diana C.

AU - Park, David J.

AU - Patel, Ravi

AU - Hu, Eddie H.

AU - Sadeghi, Saeed

AU - Parikh, Rupesh J.

AU - Reckamp, Karen L.

AU - Adams, Brad

AU - Elashoff, Robert M.

AU - Elashoff, David

AU - Grogan, Tristan

AU - Wang, He Jing

AU - Dacic, Sanja

AU - Brennan, Meghan

AU - Valdes, Yacgley

AU - Davenport, Simon

AU - Dubinett, Steven M.

AU - Press, Michael F.

AU - Slamon, Dennis J.

AU - Pietras, Richard J.

N1 - Funding Information: This work was supported by the National Institutes of Health grant numbers K23CA149079, P50 CA090440, SPORE CDA FDP-NIHCA090388, NIH CTSIUL1 TR 000124, One Ball Matt Memorial Golf Tournament, V Foundation for Cancer Research, UCLA Jonsson Comprehensive Cancer Center, Wolfen Family Lung Cancer Research Program, Stiles Program in Oncology, Hickey Foundation, National Lung Cancer Partnership, Genentech, AstraZeneca, and F. Hoffmann-La Roche Ltd. This project used the University of Pittsburgh Small Molecule Biomarker Core for analysis of estradiol and estrone. Funding Information: This work was supported by the National Institutes of Health grant numbers K23CA149079 , P50 CA090440 , SPORE CDA FDP-NIH CA090388 , NIH CTSI UL1 TR 000124 , One Ball Matt Memorial Golf Tournament , V Foundation for Cancer Research , UCLA Jonsson Comprehensive Cancer Center , Wolfen Family Lung Cancer Research Program , Stiles Program in Oncology, Hickey Foundation , National Lung Cancer Partnership, Genentech, AstraZeneca , and F. Hoffmann-La Roche Ltd . This project used the University of Pittsburgh Small Molecule Biomarker Core for analysis of estradiol and estrone. Publisher Copyright: © 2018 Elsevier B.V.

PY - 2018/9

Y1 - 2018/9

N2 - Objectives: This open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients. Materials and Methods: Patients with advanced or metastatic NSCLC, ECOG 0–2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150 mg oral daily plus 500 mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150 mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: Among 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (p = 0.77). PFS median 3.5 versus 1.9 months [HR = 0.86, 95% CI (0.52–1.43), p = 0.29] and OS median 9.5 versus 5.8 months [HR = 0.92, 95% CI (0.57–1.48), p = 0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (n = 51), but not EGFR mutant patients (n = 17), median PFS was 3.5 versus 1.7 months [HR = 0.35, 95% CI (0.14-0.86), p = 0.02] and OS was 6.2 versus 5.2 months [HR = 0.72, 95% CI (0.35–1.48), p = 0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (p = 0.03). Treatment was well tolerated with predominant grade 1–2 dermatologic and gastrointestinal adverse effects. Conclusion: Addition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.

AB - Objectives: This open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients. Materials and Methods: Patients with advanced or metastatic NSCLC, ECOG 0–2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150 mg oral daily plus 500 mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150 mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: Among 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (p = 0.77). PFS median 3.5 versus 1.9 months [HR = 0.86, 95% CI (0.52–1.43), p = 0.29] and OS median 9.5 versus 5.8 months [HR = 0.92, 95% CI (0.57–1.48), p = 0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (n = 51), but not EGFR mutant patients (n = 17), median PFS was 3.5 versus 1.7 months [HR = 0.35, 95% CI (0.14-0.86), p = 0.02] and OS was 6.2 versus 5.2 months [HR = 0.72, 95% CI (0.35–1.48), p = 0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (p = 0.03). Treatment was well tolerated with predominant grade 1–2 dermatologic and gastrointestinal adverse effects. Conclusion: Addition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.

KW - EGFR

KW - Erlotinib

KW - Estrogen

KW - Estrogen receptor

KW - Fulvestrant

KW - Lung cancer

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ER -

Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer

Abstract

Bibliographical note

Keywords

UN SDGs

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