Phase II pilot study of induction erlotinib therapy in patients with resectable non-small cell lung cancer to select postoperative adjuvant therapy

Background: Adjuvant chemotherapy has been widely accepted as the standard therapy for stage I‐IIIA NSCLC, but resulted in significant toxicity and short‐term deterioration of quality of life. In addition, not all patients can receive cytotoxic adjuvant chemotherapy. On the other hand, erlotinib demonstrated to significantly improve survival outcome for previously treated NSCLC patients regardless of their clinical characteristics. Based on those findings, we conducted a prospective pilot study of short‐term induction erlotinib to select responders who might benefit from adjuvant erlotinib therapy in patients who were scheduled to undergo surgical resection. Methods: Patients had previously untreated, potentially surgical resectable, stage IB‐IIIA NSCLC with ECOG PS of 0–1 and adequate organ functions. Induction erlotinib 150 mg once a day was administered for 28 days. Subsequently patients underwent restaging and planned surgery. Erlotinib responders, defined as their tumor shrinkage of more than 10%, would receive adjuvant erlotinib for 12 weeks while the others would receive any kind of adjuvant platinum doublets. Postoperative radiotherapy could be given in case of incomplete resection or clinician9s decision. Results: Between October 2006 and March 2009, 16 patients participated in this study; median age was 59 (41–71); 13 were male; 6 were never‐smoker; and 13 had adenocarcinoma. Preoperative clinical stage was as follows; IB 4, IIA 1, IIB 5, IIIA 6. All patients received induction erlotinib monotherapy and all but one, who declined surgery but received curative radiotherapy, underwent planned surgical resection. Out of 16 patients, 5 patients (3 PRs and 2 SDs) received adjuvant erlotinib therapy, while an adjuvant platinum doublet was given in 6, concurrent chemoradiation in 3 due to incomplete resection in 3 and no adjuvant therapy in 1 due to his pathologic stage of IA. There was no complete response. With a median follow‐up of 24 months, 8 patients progressed and 3 patient died of progressive disease. No relationships were observed between the responsiveness and biomarkers, such expression levels of VEGF, EGFR, Ki67 and P53. Additional biomarker studies are now ongoing. Conclusions: Induction erlotinib is tolerable and modestly active in patients with resectable NSCLC. The role of adjuvant erlotinib is still not defined yet, but short‐term erlotinib before curative surgical resection could predict patients who might benefit from adjuvant erlotinib therapy and avoid toxic adjuvant chemotherapy. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C41.