Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 505

J. Tsurutani¹, T. Mitsudomi², S. Mori³, I. Okamoto¹, N. Kaname⁴, H. Tada⁵, S. Negoro⁶, Y. Yatabe⁷, M. Fukuoka⁸, K. Nakagawa<sup>1

1</sup>Kinki University School of Medicine, Medical Oncology, Osakasayama, Japan
²Aichi Cacer Center, Thoracic Oncology, Nagoya, Japan
³Yokohama City University, Biostatistics and Epidemiology, Yokohama, Japan
⁴National Kyushu Cancer Center, Thoracic Oncology, Fukuoka, Japan
⁵Osaka City General Hospital, Thoracic Oncology, Osaka, Japan
⁶Hyogo Cancer Center, Medical Oncology, Akashi, Japan
⁷Aichi Cancer Center, Pathology and Molecular Diagnostics, Nagoya, Japan
⁸Kinki University School of Medicine Sakai Hospital, Medical Oncology, Sakai, Japan

Background: Patients with non-small cell lung cancer (NSCLC) harboring activating mutations of the EGFR gene respond remarkably well to EGFR specific tyrosine kinase inhibitor, gefitinib. However, its superiority to standard platinum doublet chemotherapy in terms of progression free survival (PFS) or overall survival (OS) is not known.
Material and Methods: Chemo naive patients with stage IIIB/IV or recurrent NSCLC, harboring activating EGFR mutation (either exon 19 deletion or L858R in exon 21) aged 75 years or younger, with PS of 0 or 1 were enrolled. Patients were randomized to receive either gefitinib (250 mg/day) until progression or cisplatin (80 mg/sqm) plus docetaxel (60 mg/sqm) day 1, given every 21 days for three cycles to six cycles. PFS was the primary endpoint. Assuming that PFS for gefitinib was 12.5months and for chemotherapy was 7 month based on the previous reports, hazard ratio would be 0.56. With this HR, 146 patients would be required to have a power of 0.8. However, sample size was set at 200 patients to allow HR up to 0.64.
Results: As of April 25, 164 patients had been randomized. Here, we report the preliminary data for 122 patients of the 164. Of 122, 55 patients were postoperative recurrence and 67 were with stage IIIB/IV diseases. Age, sex, stage, smoking history and absence or presence of postoperative adjuvant chemotherapy were well balanced between two groups. Percentages of the patients with age of 65 or older, female, non-smokers were 49%, 74%, and 75%, respectively. For all patients, median PFS was 8.4 months and one-year PFS rate was 32.4% (95% confidence interval (CI); 22.4–42.9%). Median survival was not reached and one-year OS rate was 94.0% (95% CI; 84.7–97.7%).
Conclusions: The enrollment of this phase III trial is ongoing. NSCLC patients with EGFR mutations had good prognosis irrespective of the treatments confirming the previous reports. Subset analysis of IPASS (Phase III study of gefitinib vs. carboplatin/paclitaxel in Asian, non-/light smokers with adenocarcinoma of the lung) suggested that NSCLC patients with EGFR mutation treated with gefitinib had a significantly longer PFS than those treated with chemotherapy with a HR of 0.48 (∼10 months vs. ∼6 months). Our study appears to have similar PFS and it would be positive if this HR is reproduced. Data on response rates and safety profile will be available at the presentation. The final analysis is expected in early 2010.