Prevalence and effectiveness of first-, second-, and third-line systemic therapy in a cohort of unselected patients with advanced non-small cell lung cancer.

Systemic therapy is the most relevant option for patients with advanced non-small-cell lung cancer (NSCLC) and many receive therapies beyond first-line. Little is known on response, progression free survival (PFS) and overall survival (OS) and their prognostic factors after second- and third-line therapy in daily clinical practice. Between January 2003 and July 2007, 406 consecutive patients were included in this prospective observational study and followed up until August 2010. At each treatment line the timing and kind of therapy, best response achieved, sites and time of progression were documented. Multiple logistic and Cox-regression models were used to analyse prognostic factors for achieving disease control (DC: response or disease stabilization), PFS and OS after different therapy lines. DC rate and median PFS decreased from 64% and 146 days, to 41% and 49 days, and to 39% and 51 days in response to first-, second- and third-line, respectively. A strong predictor for a worse outcome after second-line was development of new metastases after first-line therapy (DC: OR=2.50; 95% CI: 1.30-4.83; p-value=0.006; PFS: HR=1.53; 95% CI: 1.13-2.06; p-value=0.005) or achieving no DC after first-line (OS: HR=1.41; 95% CI: 1.01-1.97; p-value=0.041). Achieving no DC after second-line was a strong negative predictor for all outcome measures after third-line therapy (DC: OR=5.10; 95% CI: 1.56-16.6; p-value=0.007; PFS: HR=2.00; 95% CI: 1.23-3.27; p-value=0.005; OS: HR=1.69; 95% CI: 1.02-2.79; p-value=0.042). In conclusion, response in previous line and no involvement of new metastases after progression were relevant positive prognostic factors. However, further research is necessary to identify optimal therapy sequences.