Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial

Abstract

Background: Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection.

Methods: 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS).

Results: 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation.

Conclusions: Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure.

Trial registration: ClinicalTrials.gov Identifier: NCT01609543.

Keywords: EGFR; Erlotinib; Lung adenocarcinoma; Non-small cell lung cancer.

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The authors declare that they have no competing interests.

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Figures

Fig. 1

EGFR mutation status in the screened population and best response to first line erlotinib treatment. (a) Out of the 651 screened patients, 62 carried EGFR mutations including 37 in exon 19 and 35 in exon 21. (b) The distribution of best response among the 56 intent-to-treat patients. (CR – complete remission, PR – partial response, SD – stable disease, PD – progressive disease)

Fig. 2

Kaplan-Meier analysis of progression-free survival. (a) The intent-to-treat cohort had a 12.8 months median PFS. (b) Never smoker patients had increased progression-free survival. (c) Patients with extrathoracic metastasis at the time of screening had lower PFS than patients with pulmonary metastasis. (d) ECOG2 patients demonstrated progression earlier when compared to ECOG1 or ECOG0 performance status