Prospective trial with preoperative gefitinib to correlate lung cancer response with EGFR exon 19 and 21 mutations and to select patients for adjuvant therapy

Abstract

7021 Background: Induction therapy provides a unique opportunity for the objective assessment of therapies in patients with NSCLC to facilitate care and advance research. We designed this 40 patient prospective trial to measure gefitinib’s ability to induce regressions preoperatively in individuals with NSCLC and to simultaneously correlate response with mutations in EGFR exons 19 and 21. Patients with ‘in-vivo‘ gefitinib sensitivity and/or mutations receive gefitinib postoperatively as well. To facilitate our goals, we enriched the population studied to select individuals with tumors more likely to harbor mutations in EGFR. Methods: At diagnosis, patients with stage I or II NSCLC had baseline chest CT imaging and a core-needle biopsy to detect EGFR mutations. All participants smoked cigarettes ≤ 10 pack years and/or had tumors with bronchioloalveolar features. All received gefitinib 250 mg daily. After 21 days, CT imaging was repeated and resection followed. Surgical specimens were agained assayed for EGFR mutations. Patients with mutation and/or a ≥ 25% regression (WHO) were given gefitinib 250 mg for 2 years. Results: 20 patients enrolled to date. EGFR mutations were detected in both pre and post gefitinib specimens in 4/19 tested (21%). Five of 19 (26%) had a ≥ 25% bidimensional tumor reduction after 3 weeks. Regressions ≥ 25% were seen in 2/4 (50%) with exon 19 and 21 EGFR mutations and 3/15 (20%) with WT EGFR. The other 2 patients with mutations had 11% and 23% tumor regressions. The 6 patients who had either a ≥ 25% lesion reduction and/or mutation received gefitinib postoperatively. No perioperative complications related to gefitinib occurred. All patients are relapse free. Conclusions: In this ongoing trial, 1) Our ‘enrichment strategy‘ resulted in the detection of twice the expected number of EGFR mutations in USA patients with NSCLC. 2) Gefitinib sensitivity can be assessed by CT in 3 weeks. 3) Results of mutation detection were identical in pre- and post-treatment specimens. 4) The rate of response is numerically higher in patients with EGFR mutations in exons 19 and 21. 5) We are using the surgical specimens to elucidate determinants of gefitinib sensitivity in the absence of EGFR mutation. Support: CA05826, CA113653. [Table: see text]