A Multicenter Phase II Study of Gefitinib in Squamous NSCLC Patients Who Failed First-Line Chemotherapy

Abstract

Background The role of EGFR tyrosine-kinase inhibitors in the second-line for patients with squamous non-small-cell lung cancer (NSCLC) remains unclear. We conducted a prospective phase II study to assess use of gefitinib in patients with squamous NSCLC as second-line chemotherapy, and investigated the predictive and prognostic value of a proteomic signature using VeriStrat test. Methods Between December 2011 and October 2015, 56 patients with histologically confirmed, second-line, Stage IIIB or IV NSCLC were enrolled in 9 centers in Republic of Korea. Patients were treated with gefitinib (250 mg per day orally). The proteomic test classification was masked for patients and investigators. The primary end point was disease control rate (DCR) at 8-weeks, and the secondary end points included toxicity, progression-free survival (PFS), overall survival (OS), and correlation between the serum proteomic test classification and treatment. This study is registered with ClinicalTrials.gov, number NCT01485809. Results The median age was 69 years (range, 41-83) and 55 (98%) patients were male, and 49 (88%) had an ECOG PS of 1. Fifty five (98%) of patients had received platinum-based chemotherapy. The DCR at 8 weeks was 50.0% (95% confidence interval [CI] 34.8-63.4). With a median follow-up of 5.5 months, the median PFS and OS were 2.8 (95% CI 1.3-4.3) and 6.4 (5.4-7.4) months, respectively. The most common adverse event were rash (16 [29%]) and diarrhea (14 [25%]). Pretreatment plasma was available for 50 samples, and VeriStrat testing was successful in 45 samples (90%) with 71% classified as Good. The median PFS were 3.2 (95% CI 1.9-4.7) and 2.4 (1.5-3.3) months for VeriStrat Good vs. Poor patients, respectively (p=0.639). The median OS of VeriStrat Good was longer than those of VeriStrat Poor (11.4 [5.7-17.0] vs 4.8 [2.5-7.0] months), which was not statistically significant (p=0.052). Conclusion These data suggest that gefitinib is modest activity as second-line chemotherapy in patients with squamous NSCLC. Serum proteomic test using VeriStrat is not prognostic for both OS and PFS among squamous NSCLC patients treated with gefitinib.