The hypothesis tested in this study is that gefitinib / pemetrexed as maintenance therapy in patients with advanced (stage IV) EGFR mutation negative nonsquamous NSCLC who respond to 4 cycles of pemetrexed / cisplatin or pemetrexed/carboplatin as first-line therapy will achieve longer PFS than pemetrexed alone. We assume a median PFS of 4 months for patients receiving pemetrexed alone and the hazard ratio of pemetrexed alone compared to gefitinib/pemetrexed would be 0.42. It also indicates that the median PFS in gefitinib/pemetrexed group will be approximately 9.52 months. This is a 2-arm study in a 1:1 randomisation. Assuming an uniform accrual of 12-month with an addition of 12-month follow-up period, the total evaluable number of patients will be 52 to achieve a power of 80% and one-sided significance level of 0.025 to detect such difference between gefitinib/pemetrexed and pemetrexed alone.~Assuming 60% of patients respond (CR/PR/SD) to 4 cycles of pemetrexed/gefitinib, and among them 60% are EGFR mutation negative, 144 patients need to be enrolled to receive 4 cycles of pemetrexed/cisplatin or pemetrexed/carboplatin as first-line therapy.~Besides, the result of anaplastic lymphoma kinase gene (ALK) mutation will be retrospectively collected if the mutation is available for study patients during the study period.
The study aims to randomize 52 patients with advanced (Stage IV) EGFR mutation negative nonsquamous non-small cell lung cancer (NSCLC) who respond (CR/PR/SD) to 4 cycles of pemetrexed / cisplatin or pemetrexed/carboplatin as first-line therapy. In order to achieve that, approximately 144 treatment naïve patients with advanced nonsquamous NSCLC need to be enrolled from around 6 investigational sites in Taiwan that have expertise in lung cancer diagnosis.