Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC.This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1.Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1 % (27/38) (95 % confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8 %) underwent successful R0 resection. Thirty (75.0 %) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5 %) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n = 20 [50 %]), diarrhea (n = 12 [30 %]), and oral ulceration (n = 12 [30 %]).The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC.