Fulvestrant Plus Erlotinib May Improve Progression-Free Survival in EGFR Wild-Type NSCLC

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Recent findings identified interactions between the EGFR and estrogen receptor signaling pathways, which could potentially modify outcomes in non-small cell lung cancer.
Recent findings identified interactions between the EGFR and estrogen receptor signaling pathways, which could potentially modify outcomes in non-small cell lung cancer.

Fulvestrant plus erlotinib may prolong progression-free survival (PFS) among patients with EGFR wild-type (EGFR WT) non-small cell lung cancer (NSCLC) compared with erlotinib alone, according to a study published in Lung Cancer.1

EGFR inhibitor monotherapy has been associated with improved outcomes among patients with EGFR-mutant NSCLC, but efficacy among EGFR WT-NSCLC is lacking. Previous studies assessing EGFR combination therapies did not lead to superior results, but recent findings revealed the interactions between the EGFR and estrogen receptor (ER) signaling pathways, which could potentially modify outcomes.

For this phase 2 study (ClinicalTrials.gov Identifier: NCT00100854), researchers randomly assigned 106 patients with advanced or metastatic NSCLC to oral erlotinib 150 mg with or without intramuscular fulvestrant 500 mg. Eligible patients had progressive disease after 1 or more standard chemotherapy regimens or refused chemotherapy, and had not received prior EGFR-directed therapies.

Results showed that the overall response rate was 16.4% and 12.1% among patients who received the combination treatment and erlotinib alone, respectively (P = .77). The median PFS was 3.5 months among patients treated with the combination versus 1.9 months for erlotinib alone (hazard ratio [HR], 0.86; 95% CI, 0.52-1.43; P = .29), and the median overall survival (OS) was 9.5 months for the combination versus 8.5 months for erlotinib alone (HR, 0.92; 95% CI, 0.57-1.48; P = 0.74).

An unplanned subset analysis however, revealed that EGFR WT patients treated with the combination therapy had a significantly prolonged PFS with 3.5 months versus 1.7 months among patients who received erlotinib alone (HR, 0.35; 95% CI, 0.14-0.86; P = 0.02). The median OS was 6.2 months versus 5.2 months among patients treated with the combination and erlotinib alone respectively (HR, 0.72; 95% CI, 0.35-1.48; P = 0.37). Interestingly, 50% of patients who were EGFR WT were also hormone-receptor positive, compared with just 9.1% of EGFR-mutated patients (P = .03).

The majority of adverse events (AE) were limited to grade 1 or 2 dermatologic or gastrointestinal toxicities. The most commonly observed grade 3 to 4 AEs were diarrhea, rash, anorexia, and/or fatigue.

Reference

  1. Garon EB, Siegfried JM, Stabile LP, et al. Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer [published online June 22, 2018]. Lung Canc. doi: 10.1016/j.lungcan.2018.06.013

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