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Lung Cancer. 2018 Sep;123:91-98. doi: 10.1016/j.lungcan.2018.06.013. Epub 2018 Jun 22.

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

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David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA, USA. Electronic address:
University of Minnesota, Masonic Cancer Center, 420 Delaware Street SE, NHH 3-112, CCRB 3-130 Minneapolis, MN 55455, USA.
University of Pittsburgh Cancer Institute, Department of Pharmacology & Chemical Biology, 5117 Centre Avenue, Lab 2.7, Pittsburgh, PA 15232, USA.
David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA, USA.
St. Jude Heritage Healthcare, Virginia K. Crosson Cancer Center, 2151 N. Harbor Boulevard, Suite 2200, Fullerton, CA 92835, USA.
Comprehensive Blood and Cancer Center, 6501 Truxtun Avenue, Bakersfield, CA 93309, USA.
Comprehensive Cancer Care Centers of Nevada, 10001 So. Eastern Ave., Suite 108, Henderson, NV 89052, USA.
City of Hope, 1500 E Duarte Rd, Duarte, CA 91010, USA.
Translational Research in Oncology, 8-684 Factor Building, Box 951781, 90095-1781 Los Angeles, CA, USA.
University of Southern California School of Medicine and Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Los Angeles, CA 90089, USA.



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.


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).


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.


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.


EGFR; Erlotinib; Estrogen; Estrogen receptor; Fulvestrant; Lung cancer

[Available on 2019-09-01]

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