Differential efficacy of pemetrexed in nonsquamous NSCLC based on human cytokeratin fragment antigen 21-1 (CYFRA21-1) serum levels.

Abstract

10612 Background: Recent clinical trials demonstrate that histology is an important factor in NSCLC for individualized treatments based on safety or efficacy outcomes. However, several problems persist with histology-based treatments. The main problem is that it is difficult to obtain adequate biopsy specimens to accurately distinguish the histological subtypes of NSCLC. Therefore, a more objective, yet simple biomarker for histology-based treatment is needed. Human cytokeratin fragment antigen 21-1 (CYFRA21-1) is one of the tumor markers for NSCLC and may be representative of the squamous subtype. In this study, we examined whether serum CYFRA21-1 levels were associated with the efficacy of pemetrexed in NSCLC. Methods: From September 2009 to December 2010, 46 previously treated NSCLC patients who received pemetrexed monotherapy (500 mg/m2 every 3 weeks) until disease progression were evaluated. Serum concentrations of CYFRA21-1, CEA, SCC, and sialyl Lewis X-i antigen (SLX) were measured. We analyzed possible associations between these NSCLC marker levels and pemetrexed treatment efficacy. Results: Patient characteristics were: male/female = 22/24; median age = 63 yrs. (34-79 yrs.); histology: adeno/large/NOS = 42/2/2; PS: 0/1/2/3= 25/19/1/1. For these 46 patients, elevated levels of serum CYFRA21-1, CEA, SCC, and SLX were found in 18, 30, 12, and 33 patients, respectively. PFS for patients with elevated serum CYFRA21-1 was significantly shorter than for patients without elevated serum CYFRA21-1 (median PFS: 81 vs. 111 days; P=0.035), whereas no significant differences in PFS were observed for CEA, SCC, or SLX levels. Conclusions: Serum CYFRA21-1 levels are associated with the efficacy of pemetrexed in NSCLC and may be a predictive marker for pemetrexed use. We are planning a larger scale study to confirm this observation.