Efficacy and safety of fosaprepitant in the prevention of nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study.

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.

Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study.

INTRODUCTION: This randomized, open-label study compared pemetrexed versus docetaxel as second-line therapy for Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint tested non-inferiority of overall survival (OS) on the combined data from these patients and those in the global registration trial. Data from patients in the current study only (Chinese patients) were the basis for the study's secondary objectives. METHODS: Patients with stage IIIB/IV disease were randomized (1:1) to receive pemetrexed (500 mg/m(2); 107 randomized; 106 treated) or docetaxel (75 mg/m(2); 104 randomized; 102 treated) on Day 1 of each 21-day cycle. Treatment continued until progressive disease, unacceptable toxicity or patient/investigator decision. All efficacy and safety data were analyzed at the pre-specified study completion; supplementary OS analyses were performed later, after additional events had been recorded. RESULTS: The primary endpoint of OS noninferiority of pemetrexed to docetaxel was not met, the lower CL was <50% and P>0.025 (efficacy retained=97.9% [95% CLs: 47.1, 141.9]; P=0.0276), in the combined population (pemetrexed: n=390, docetaxel: n=392). Supplementary values were 101.3% (95% CLs: 57.9, 148.8), P=0.0186. For the secondary objectives, assessed in the population from the current study (pemetrexed: n=107, docetaxel: n=104), median OS was 11.7 and 12.2 months for the pemetrexed and docetaxel arms, respectively (HR [95% CLs]: 1.14 [0.78, 1.68], P=0.492). Supplementary values were 11.4 and 11.5 months, respectively (HR [95% CLs]: 1.02 [0.74, 1.40], P=0.926). Median PFS values were 2.8 and 3.1 months (HR [95% CLs]: 1.05 [0.75, 1.46], P=0.770) and ORR values were 9.6% and 4.1% (odds ratio [95% CLs]: 2.50 [0.76, 8.25], P=0.133) for pemetrexed and docetaxel, respectively. Pemetrexed-treated patients had significantly fewer drug-related grade 3-4 adverse events (pemetrexed: 20.8%, docetaxel: 40.2%; P=0.003). Few drug-related serious adverse events were reported (pemetrexed: 5 patients, docetaxel: 8 patients). CONCLUSION: The comparable efficacy and superior tolerability of pemetrexed compared with docetaxel in this study supports the use of single-agent, second-line pemetrexed for advanced non-squamous NSCLC in Chinese patients. ClinicalTrials.gov: NCT00391274.