Maintenance pemetrexed plus best supportive care (BSC) versus placebo plus BSC: A phase III study

The Differential Efficacy of Pemetrexed According to NSCLC Histology: A Review of Two Phase III Studies

“…A significant treatment-by-histology interaction for pemetrexed was also observed in a third phase III study comparing pemetrexed with placebo [10], thereby eliminating the potential that the treatment-by-histology effect is a function of the comparator drug rather than pemetrexed. The consistency of these results across studies confirms that the treatment advantage for pemetrexed in patients with nonsquamous histology is reproducible and valid.…”

“…A recent analysis of pooled data from two phase II pemetrexed trials also showed histology effects for pemetrexed [11]. In another recent phase III study of pemetrexed versus placebo as maintenance therapy following frontline treatment, a prespecified analysis of efficacy by histology showed significant differences in RRs, PFS, and preliminary OS according to histologic subtype [10].…”

“…Response rates (RRs) for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are higher in patients with a histologic diagnosis of adenocarcinoma [6] as well as in females, Asians, and never-smokers [7,8]. Recently, a predictive role for histology was reported in three pemetrexed studies in advanced NSCLC [4,9,10], which was further supported by phase II studies [11,12].…”

Potential Treatment Options After First-Line Chemotherapy for Advanced NSCLC: Maintenance Treatment or Early Second-Line?

“…However, although overall survival trended in favor of immediate docetaxel therapy, the overall survival results did not reach statistical significance. A very relevant phase III, randomized trial was presented by Ciuleanu et al [28] at the most recent ASCO meeting. In that double-blind phase III trial, the authors compared the efficacy and safety of pemetrexed with those of placebo in patients with stage IIIB/IV NSCLC who had not progressed on four cycles of platinum-based induction chemotherapy (gemcitabine or docetaxel or paclitaxel plus cisplatin or carboplatin).…”

“…The authors concluded that continuing third-generation chemotherapy beyond three or four cycles resulted in a significantly longer progression-free survival time but not overall survival time, and produced more adverse events. However, in un update presented at the last ASCO meeting, Soon et al [34] updated the data, including the results of the trial of Ciuleanu et al [28] on maintenance treatment with pemetrexed. Considering these data, Soon et al [34] showed a statistically significant benefit in terms of overall survival (HR, 0.92; 95% CI, 0.86 -0.99; p ϭ .03) in favor of prolonged chemotherapy, but this delayed adjunct of data to the original meta-analysis presents a methodological issue.…”