Efficacy of Chemotherapy (CHT) Beyond Tyrosine Kinases Inhibitors (TKI) in Advanced Non Small Cell Lung Cancer (NSCLC) Patients (PTS) Unselected for Epidermal Growth Factor Receptor (EGFR) Mutation

ABSTRACT Background After failure of a second or third line therapy with TKI, many clinicians offer to their advanced NSCLC pts a new line of cht, even if there are no perspective trials that support this choice. We report our experience about cytotoxic treatment administered after a target therapy with Erlotinb or Gefitinib in pts with unknown EGFR mutational status or EGFR wild type. Patients and methods Since January 2003 to December 2011, 84 pts received TKI in second or third line and after progression 34 of them were treated with at least one subsequent line of cht. We collected response data, analyzed overall survival (OS) and progression free survival (PFS) of cht beyond TKI with Kaplan-Meier method and correlated them with Disease Control (DC) and PFS of first line cht and TKI using log-rank test. Results 29 out of 34 pts received cht as third and 5 pts as forth line treatment. 67,6 % of pts received a monotherapy, while 32,4% a combination treatment, platinum based in 7 cases. A response rate (RR) of 20,5% and a DC rate of 52,9% were registered. Median OS post-TKI and PFS were 13 (95% C.I. 6,36-19,63) and 3 months (mos) (95% C.I 0,5-5,5) respectively. OS of pts who obtained DC during TKI was 18,2 mos compared to 5,7 mos of pts not responder to target treatment (p = 0,019). At univariate analysis good PS(≤1) after TKI (p = 0,022), DC (p = 0,025) and PFS > 6 mos with first line cht(p = 0,002) were found to be the only predictive factors of a better PFS with post-TKI cht. At multivariate analysis only the PFS > 6 mos with first line cht was confirmed as an independent predictive factor of better PFS in post-TKI setting (p = 0,05). Age more or less than 65 years (p = 0,7) use of combination (p = 0,84) and platinum-based therapy (p = 0,75) seems not to improve survival outcome and DC of cht beyond TKI. Conclusions DC with TKI identify a good prognostic group of pts. Good and prolonged response (> 6 mos) to the first line cht and a PS ≤1 are useful predictive factors to select pts who could benefit from receiving a cytotoxic treatment after target agents failure. Aggressive cht strategies do not seem to produce a real advantage in this setting. Disclosure All authors have declared no conflicts of interest.