OBJECTIVES: Second-line monotherapy options for advanced NSCLC include erlotinib (E), docetaxel (D), or pemetrexed (P), The purpose of this retrospective study was to compare economic outcomes among patients (pts) receiving 2nd line monotherapy in the outpatient community setting. METHODS: Using US Oncology’s iKnowMed EMR data, we identified advanced NSCLC patients who received 2nd line monotherapy from July 1, 2006 – June 30, 2008. Economic outcomes were derived using outpatient claims and pharmacy data and included total outpatient, chemotherapy, supportive care costs, and frequency of outpatient physician visits, lab procedures, and acute care (ER/inpatient) visits. All economic outcomes were calculated as per-patient month (PPM) metrics over a 12 month follow-up period. Multiple regression analyses were used to estimate the independent association between treatment (E, D, or P) on outcomes after controlling for age, gender, stage at diagnosis, baseline hemoglobin, and performance status. RESULTS: We identified 610 pts – 73 received E, 87 received D, and 450 received P.  Total cost, chemotherapy costs, and supportive care costs differed significantly by treatment, as did frequency of outpatient visits and lab procedures. Relative to P, total adjusted costs PPM is $1579 lower for D and $1584 lower for E (p<0.05).  Majority of the cost savings are due to decreased chemo-related costs.  Outpatient visits, lab procedures and acute care visits are also less frequent with E relative to P (-2.6 PPM, p<0.05). CONCLUSIONS: In US outpatient setting, pts receiving E and D have statistically significant lower costs and resource use relative to pts receiving P.