A phase II study of gefitinib monotherapy for chemotherapy-naive patients with non-small cell lung cancer

Abstract

7074 Background: Gefitinib is effective as a 2nd or 3rd line treatment for non-small cell lung cancer (NSCLC), but efficacy for chemotherapy-naïve patients (pts) with NSCLC has not been established. Recently, EGFR gene mutation reported to be a predictor of response to gefitinib. Methods: We conducted a phase II study evaluating the efficacy and safety of gefitinib in chemotherapy-naïve NSCLC. The primary endpoint was response rate (RR). We also investigated whether the15-bp deletion of EGFR (E746 A750del) could be observed in serum DNA and served as a noninvasive source of information of genotype of tumor cells. Eligibility criteria were stage IIIB or IV chemotherapy-naïve NSCLC, PS 0–2, measurable lesion(s), age ≥20 years-old, adequate organ functions, and written informed consent. This study, with a sample size of 25, had 80% power to support the hypothesis that the true RR was >30%, and 5% significance to deny the hypothesis that true RR was <10%. If 5 or more of 25 pts responded, gefitinib was concluded to be effective. Assuming an inevaluability rate < 20%, we projected an accrual of 30 pts. Results: From Oct. 2002 to Aug, 2003, 30 pts were enrolled and all 30 pts were eligible. The RR was 33.3% (95% CI, 16.2–49.8%) and disease control rate of 63.3% (95% CI, 46.0–80.5%). Median time to progression (TTP) was 3.3 months (0-3-23), median overall survival was 10.0 months (1.7–26) and 1-year survival rate was 43.3% (median follow-up, 13 months). Grade 3 toxicities were observed in 7 pts (2 skin, 1 diarrhea, 2 liver, and 2 lung). Both E746 A750del (10/27) and wild-type EGFR (22/27) were detected in pretreatment samples. No correlations were seen between presence of E746 A750del in pretreatment samples and response or gender. E746 A750del was significantly more frequent in post-treatment samples from pts with PR and SD than in pts with PD (p<0.05), and correlated with TTP (p<0.05). Conclusions: Gefitinib in chemotherapy-naïve NSCLC was active with acceptable tolerability. E746 A750del in circulating tumor cells was detectable in serum samples. While E746 A750del in serum of untreated pts was not a predictor of gefitinib response, detection of E746 A750del correlated with disease control and TTP. No significant financial relationships to disclose.