This did not appear to be fully explained by a differential increase in toxicity, nor did it appear to be related to differences in dose intensity or changes in exposure to ramucirumab or docetaxel

This did not appear to be fully explained by a differential increase in toxicity, nor did it appear to be related to differences in dose intensity or changes in exposure to ramucirumab or docetaxel. There have been a significant number of publications related to the use of bevacizumab in the elderly [15C20]. frequent (5%) grade 3 and 4 adverse reactions in the ramucirumab arm were fatigue, neutropenia, febrile neutropenia, leukopenia, and hypertension. Implications for Practice: This report presents TPA 023 key information on the U.S. Food and Drug Administration approval of ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2, given in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer whose disease has progressed on or after platinum-based chemotherapy. This report specifically addresses the issues of safety in patients with squamous cell tumors, effect of treatment in elderly patients, and uncertainties regarding effects in patients with tumors harboring epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations. value of .025 using the stratified log-rank test. Results A total TPA 023 of 1 1,825 patients were screened at 216 sites worldwide; 572 patients were excluded (486 did not meet study criteria, 71 decided not to participate, 9 died, and 6 were excluded for other reasons). TPA 023 The intention-to-treat population consisted of 1,253 patients randomly allocated to ramucirumab plus docetaxel (= 628) or placebo plus docetaxel (= 625). There were 912 patients with nonsquamous cell histology, 328 with squamous cell histology, and 13 with unknown histology. EGFR mutation status was known for only 437 patients (36%); of these, 33 (8%) had tumors harboring an EGFR mutation. ALK rearrangement status was not assessed in this study. The median duration of treatment was 4.5 MMP10 months (range: 0.7C27 months) for ramucirumab plus docetaxel and 3.8 months (range: 0.7C30 months) for placebo plus docetaxel. Overall, baseline demographic and stratification factors were similar between the TPA 023 two treatment arms. There was a slight imbalance in smoking status, with fewer never-smokers in the ramucirumab arm versus the placebo arm (17% vs. 23%). There was also a slight imbalance in histology, with a lower percentage of patients with squamous histology in the ramucirumab arm versus the placebo arm (25% vs. 27%). The proportion of elderly patients (age 65 years or older) was 38% in the ramucirumab arm and 35% in the placebo arm. Efficacy Patients treated with the combination of ramucirumab plus docetaxel had a longer OS compared with patients treated with placebo plus docetaxel, with a median OS of 10.5 months versus 9.1 months, respectively (HR: 0.86; 95% CI: 0.75, 0.98; = .024) (Fig. 1). A statistically significant 1.5-month improvement in median PFS was also documented for the ramucirumab plus docetaxel arm compared with the placebo plus docetaxel arm (median PFS: 4.5 months vs. 3.0 months, respectively; HR: 0.76; 95% CI: 0.68, 0.86; .001). ORR was 23% for the ramucirumab plus docetaxel arm and 14% for the placebo plus docetaxel arm ( .001). Open in a separate window Figure 1. Kaplan-Meier curves of overall survival in the intention-to-treat TPA 023 population. Abbreviations: Doc, docetaxel; Plac, placebo; Ram, ramucirumab. During sBLA review, the FDA performed several exploratory subgroup analyses. The FDA was particularly interested in treatment effects by age, EGFR mutational status, histology, and prior therapy with a taxane or bevacizumab (Table 1). Table 1. Exploratory subgroup analyses Open in a separate window = 33), the treatment effect also appears to have been preserved in this subgroup. For the exploratory subgroup analysis of patients age 65 years or older, there did not appear to be a treatment effect with the addition of ramucirumab to docetaxel in terms of PFS or OS. Safety Of the 1,253 patients in the REVEL study, 1,245 received at least 1 dose of protocol-specified therapy and were included in the analysis of safety. Eight patients were not treated for the following reasons: previous adverse event (= 3), did not meet protocol entry criteria (= 2), declined to participate (= 2),.