P2.03a-004 Second-line Therapy Improves Overall Survival in Primary Refractory Non Small-Cell Lung Cancer (NSCLC) Patients

Abstract

The effect of palliative chemotherapy for non-small cell lung cancer (NSCLC) is well established. However, little is known on the efficacy of cytotoxic chemotherapy in patients whose tumors are refractory to first-line chemotherapy. We analyzed the outcome of all consecutive and unselected patients receiving palliative chemotherapy in a single institution to assess the efficacy of second-line chemotherapy in primary refractory NSCLC. 462 consecutive patients with palliative treatment for NSCLC at the University Hospital Basel between 1990 and 2009 were analyzed. Measured outcomes were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients with progressive disease (PD) as best response to first-line treatment were compared to patients with stable disease (SD), partial (PR) or complete remission (CR). Chi-square test was used for discrete, and Mann Whitney U tests for continuous variables, respectively. Probabilities of survival were calculated using the Kaplan-Meier estimator. The log-rank test was used for comparing groups. Median age was 63 years, 71% were male, 81% were smokers and 53% had adenocarcinoma. Median OS of the whole cohort was 11.3 months. 62.3% of patients were treated with a platinum-based (48.3% cisplatin-based) first-line therapy. Median PFS for first-line therapy was 3.0 months. 192 patients (41.6%) were primary refractory on first-line therapy. Median OS was significantly shorter for refractory patients compared to patients with CR, PR or SD (9.2 vs. 14.5 months, p<0.0001). Poorer initial performance status was significantly associated with primary refractory disease (p=0.015). All other baseline characteristics did not differ between refractory and responding patients. 67 (35%) primary refractory patients received a second-line therapy. The clinical benefit rate (CR+PR+SD) from second-line therapy was lower in primary refractory patients (33.9% vs. 43.5%, p=0.023). Median PFS for second-line therapy was shorter for primary refractory patients (2.2 vs. 4.6 months, p=0.26). Median OS was significantly longer for refractory patients receiving second-line chemotherapy vs. best supportive care (13.6 vs. 5.5 months, p<0.0001). More than 40% of patients are primary refractory to palliative first-line therapy. These patients have a poor prognosis. However, active second-line chemotherapy can significantly improve the outcome compared to best supportive care. Median OS for patients receiving second-line chemotherapy was close to patients with initial response or stable disease. Patients with primary refractory NSCLC should be offered further active therapy. These real life data for primary refractory patients form the basis against which immunotherapies, the current standard second line treatment, can be compared.