Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR-mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial
Mené en Chine sur 102 patients atteints d'un cancer du poumon non à petites cellules de stade IIIA présentant une mutation EGFR, cet essai de phase II compare l'efficacité, du point de vue de la survie sans maladie à 2 ans, et la toxicité de l'erlotinib et d'une chimiothérapie à base de vinorelbine et de cisplatine (durée médiane de suivi : 33 mois)
Background : Adjuvant chemotherapy after radical resection of stage IIIA non-small-cell lung cancer (NSCLC) has quite poor outcomes. We aimed to investigate whether adjuvant erlotinib therapy improves 2-year disease-free survival compared with chemotherapy in epidermal growth factor receptor ( EGFR) mutation-positive stage IIIA NSCLC. Methods : In this randomised, open-label, phase 2 trial, eligible patients aged 18–75 years who had undergone complete (R0) resection of histologically or pathologically confirmed stage IIIA EGFR mutation-positive NSCLC and had not received any previous anticancer therapies were enrolled. Patients were randomly assigned (1:1) to receive either adjuvant erlotinib (150 mg once daily administered orally) or vinorelbine and cisplatin chemotherapy (four cycles of vinorelbine [25 mg/m 2 intravenously on days 1 and 8 of each 21-day cycle] plus cisplatin [75 mg/m 2 intravenously on day 1 of each 21-day cycle]). Randomisation was done by Simon's minimisation with a random element and was stratified by EGFR activating mutation type (exon 19 vs 21), histology (adenocarcinoma vs non-adenocarcinoma), and smoking status (smoker vs non-smoker). The primary endpoint in the unblinded intention-to-treat analysis was 2-year disease-free survival. This ongoing study is registered with ClinicalTrials.gov, number NCT01683175. Findings : Between Sept 8, 2012, and May 21, 2015, 102 patients from 16 centres across China were enrolled and randomly assigned to receive erlotinib (n=51) or chemotherapy (n=51). Median follow-up was 33·0 months (IQR 17·8–43·1). 2-year disease-free survival was 81·4% (95% CI 69·6–93·1) in the erlotinib group and 44·6% (26·9–62·4) in the chemotherapy group (relative risk 1·823 [95% CI 1·194–2·784; p=0·0054). The difference in 2-year disease-free survival between the groups was 36·7% (95% CI 15·5–58·0; p=0·0007). Adverse events of any grade occurred in 29 (58%) of 50 patients in the erlotinib group and 28 (65%) of 43 patients in the chemotherapy group. Grade 3 or worse adverse events occurred in six (12%) of 50 patients in the erlotinib group versus 11 (26%) of 43 in the chemotherapy group; the most common of these in the erlotinib group was rash (in two [4%] of 50 patients) and in the chemotherapy group were decreased neutrophil count (in seven [16%] of 43 patients) and myelosuppression (in four [9%]). No treatment-related deaths were reported. Interpretation : Adjuvant erlotinib improved 2-year disease-free survival in patients with EGFR mutation-positive stage IIIA NSCLC compared with chemotherapy, with a better tolerability profile. This study suggests that tyrosine kinase inhibitors could have a potentially important role as adjuvant therapy in EGFR mutation-positive stage IIIA NSCLC. However, this trial was a phase 2 study. Mature overall survival data are also needed. Ongoing studies will hopefully confirm the role of adjuvant EGFR tyrosine kinase inhibitor therapy in patients with NSCLC.