Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially Guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: The standard therapy after failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in advanced non-small cell lung cancer (NSCLC) has not yet been established. The aim of the current study was to identify whether the 2(nd) TKI treatment or chemotherapy (paclitaxel-containing or non-paclitaxel regimen) is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKIs.

METHODS: Seventy-two advanced NSCLC patients who had accepted 2(nd) TKIs or chemotherapy immediately after failure of the initial TKIs in non-first line setting from May 1, 2004 to January 31, 2010 at the Sun Yat-sen University Cancer Center were enrolled. The primary endpoint [2(nd) progression-free survival (PFS)] and the second endpoint [overall survival (OS)] were compared among the 2(nd) TKI and chemotherapy groups as well as their subgroups.

RESULTS: (1) Twenty-one patients were treated with 2(nd) TKIs, and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment. There was nonsignificant difference in the responses (P=0.900) [2(nd) PFS (P=0.833) and OS (P=0.369)] between the 2(nd) TKI and chemotherapy groups. (2) In the 2(nd) TKI group, 9 patients exhibited PFS≥7 months. The initial TKI treatment group exhibited a longer 2(nd) PFS than the other 12 patients with an initial PFS<7 months (7 months vs. 2 months, P=0.019). However, these groups had nonsignificantly different OS (P=0.369). (3) In the chemotherapy group, patients with PFS<5 months exhibited longer 2(nd) PFS than those with PFS ≥ 5 months in the initial TKI treatment (3 months vs. 2 months, P=0.039). (4) In the chemotherapy group, patients treated with paclitaxel-containing regimen showed longer 2(nd) PFS than those treated with non-paclitaxel regimen (5 months vs. 2.3 months, P=0.043).

CONCLUSIONS: Patients with PFS≥7 months or <5 months under the initial TKI treatment potentially benefit from the 2(nd) TKI treatment or chemotherapy immediately after failure of the non-first line TKIs. The paclitaxel-containing regimen may improve the 2(nd) PFS. However, more patient samples are urgently needed to validate these findings.