8087 Background: 3WD was the reference standard for second-line treatment of A-NSCLC after demonstrating improved outcome over supportive care. RCTs with 3WD as a comparator were conducted, including single agent chemotherapy (SAC) (vinorelbine/ifosfamide, pemetrexed, vinflunine, oral topotecan) and gefitinib (G). The evaluation of 3WD as current standard is needed. Methods: Survival Hazard Ratios (HRs) were extracted from papers; Peto-Odds Ratio (OR) with 95% confidence interval (CI) were derived. Heterogeneity testing was applied. Absolute differences (AD) and the Number of patients Needed to Treat (NNT) were calculated. End-points were overall survival (OS) and overall response rate (ORR). A sensitivity analysis into 2 sub-groups according to comparator (SAC or G) and 3WD dose was performed. Different toxicity patterns did not allowed to analize overall tolerability, except for neutropenia. Quality of life was compared descriptively since different scales were used across studies (LCSS in 3 RCTs, FACT-L in 4 RCTs, and TOI scale in 2 RCTs). Results: 6 RCTs (4 SAC/3 G) with 4,291 patients were analyzed (table). When grouping by 3WD dose (75mg/m2 vs 60mg/m2), G-ORR was no longer significant (OR 1.15, 95% CI 0.80, 1.65; p=0.447). Grade 3–4 neutropenia was higher in 3WD arms when compared with SAC, with an AD of 12.9% which corresponds to a NNT of 7, although heterogeneous (p<0.0001). In terms of QoL, 4 trials favored comparators over 3WD in global scores (3 were G studies); in only 1 of these were differences ≥ 10%. Conclusions: This meta-analysis validates the ongoing role of 3WD as a reference standard for second-line therapy in A-NSCLC. In unselected patients, comparator agents have failed to demonstrate superiority in efficacy outcomes over 3WD. No major QoL differences were noted. However, a significant worst neutropenia is determined by 3WD, suggesting a restricted use in clinical practice. Pts (#RCTs) HR/OR (95% CI) p Het. (p) AD (%) NNT OS Overall 4,043 (6) 1.04 (0.97, 1.12) 0.20 0.64 - - SAC 1,947 (3) 1.05 (0.95, 1.16) 0.27 0.26 - - G 2,096 (3) 1.03 (0.93, 1.15) 0.48 0.74 - - ORR Overall 4,291 (7) 1.14 (0.91, 1.43) 0.24 0.04 - - SAC 2,195 (4) 0.84 (0.58, 1.22) 0.38 0.16 - - G 2,096 (3) 1.38 (1.03, 1.86) 0.029 0.15 2.8 35 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly, Roche, sanofi-aventis
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