A Phase III Open label Randomized control study to compare efficacy and safety of Pemetrexed-Carboplatin versus Paclitaxel-Carboplatin as induction regimen in advanced Non-squamous Non-Small-Cell lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC), accounts for about 85% of all lung cancers. Platinum base chemotherapy is the standard first-line treatment for patients of advanced NSCLC who are negative for the EGFR mutation and ALK rearrangement. There are

various Cisplatin and Carboplatin based regimen approved for treatment of this group. To know which regimen is better Schiller et al, conducted a randomized clinical trial. In this trial they compared the efficacy of four doublet regimens Cisplatin plus gemcitabine, cisplatin plus docetaxel, carboplatin plus paclitaxel, or cisplatin plus paclitaxel in patients with advanced non–small-cell lung cancer. None of four chemotherapy regimens offered a significant advantage over the others. In a phase III study Scagliotti et al. found that pemetrexed plus cisplatin was noninferior to gemcitabine plus cisplatin in unselected patients with advanced-stage NSCLC. On subgroup analysis survival was significantly superior for patients with non-squamous histology who were treated with pemetrexed plus cisplatin. In phase III RCT (Point Break trial) Patel et al. compared the efficacy and safety of pemetrexed plus carboplatin plus bevacizumab followed by pemetrexed plus bevacizumab with paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab in patients with advanced nonsquamous non–small-cell lung cancer. There was no difference in overall survival but PFS was significantly improved with PemCBev.  There is no trial that has compared efficacy and safety of Paclitaxel-Carboplatin versus Pemetrexed-Carboplatin. In current study we will compare the efficacy and safety of Pemetrexed-Carboplatin versus Paclitaxel-Carboplatin as induction regimen in advanced Non-squamous Non-Small-Cell lung cancer. We hypothesized that in advanced non-squamous NSCLC, four cycles of induction chemotherapy with pemetrexed and carboplatin is superior to 4 cycles of paclitaxel and carboplatin in terms of progression free survival. Several clinical trials have shown that maintenance chemotherapy is beneficial in non squamous NSCLC. Several recent studies reported that low TYMS expression was associated with better response and/or survival when treated with pemtrexed-based regimens in NSCLC patients. But some other studies did not show the significant association between TYMS expression and efficacy of pemtredxed-based chemotherapy in NSCLC. Folate receptor alpha is a glycosyl phosphatidyl inositol (GPI) anchored cell surface protein that assists in uptake of antifolates via receptor-mediated endocytosis. Some studies reported that High FRA expression associated with better response to pemetrexe. In our study we will also assess role of TS level and FRA level as predictive biomarker.