8092 Background: Chronic systemic inflammation is a well recognized strong adverse prognostic factor in advanced NSCLC. We have previously identified that in stage IIIB/IV NSCLC the presence of elevated C-reactive protein is associated with early progression of the disease and reduction in median survival. Little is known, however, about CRP behavior over time and its correlation with response to chemotherapy and survival. Methods: Newly diagnosed NSCLC with IIIB/IV disease had CRP measured prior to 1st treatment and after 2 cycles of chemotherapy between February 2005 and September 2008. For each measure CRP level was categorized as < 10mg/L or ≥10mg/L. Response was evaluated by chest CT following two cycles of CTX and rated as progression (PD) or freedom from progression (FFP). We investigated the association between change in CRP and response to 2 cycles of CTX, as well as survival. Results: 143 pts were enrolled. Of those, 62 patients had a CRP level <10mg/L and 81 patients ≥10mg/L at the time of diagnosis. After 2 cycles 70% and 72% of pts in each category remained in the same category and 30% and 28% of patients changed category: in 24/81 pts CRP decreased below 10mg/L and in 17/62 pts CRP increased above 10mg/L. Thus, after two cycles 69 pts had CRP <10mg/L and 74 pts ≥10mg/L. The rate of progression after 2 cycles was significantly lower among pts with CRP <10mg/L after 2 cycles of chemo ( Table ). Median survival was 19 (16–22) mo for those with CRP <10mg/L and 9.3 (7.1–11.4) mo for those with CRP ≥10mg/L after 2 cycles (P<0.001). The hazard increased by 66% (HR 1.7) for those pts with CRP increased above cut-off point of 10 mg/L and decreased by 60% (HR 1.6) for pts whose CRP decreased below cutoff point. Conclusions: The presence of an inflammatory state expressed by high levels of CRP either prior to treatment or following 2 cycles of chemotherapy correlates significantly with both first-line chemotherapy response and survival. Normalization of CRP might improve the prognosis of patients in terms of survival and response to chemotherapy. [Table: see text] No significant financial relationships to disclose.