Comparable activity with oral topotecan/cisplatin (TC) and IV etoposide/cisplatin (PE) as treatment for chemotherapy-naïve patients (pts) with extensive disease small cell lung cancer (ED-SCLC): Final results of a randomized phase III trial (389)

Abstract

7003 Background: TC is a tolerable regimen and requires fewer clinic visits for drug administration (Proc. ASCO 2004). A randomized phase III study comparing TC vs PE, the current standard of care, was conducted to compare safety and efficacy in this setting. Methods: Chemotherapy-naïve patients with ED-SCLC and performance status (PS) ECOG 0, 1, or 2 stratified by gender, PS, LDH, and country were randomized to receive either oral topotecan (d1–5: 1.7 mg/m2)/cisplatin (d5: 60 mg/m2) (TC) or IV etoposide (d1–3: 100 mg/m2)/cisplatin (d1: 80 mg/m2) (PE). The initial TC dose regimen, T=2.0 mg/m2/day, was reduced due to excessive, serious neutropenia, diarrhea and typhilitis. Following this amendment, a complete, randomized population at the reduced T dose, 1.7 mg/m2/day, was recruited. Primary endpoint was overall survival. Results: Between 5/2001 and 12/2002, 859 patients were recruited, 784 into the T(1.7)C and PE arms (ITT). Baseline characteristics were balanced. Median number of cycles (range) for TC was 5 (1–9), PE 6 (1–8). TC and PE were well tolerated. Hematologic toxicity, TC vs PE: G4 neutropenia (26, 56.8%), Gr 4 thrombocytopenia (8.7, 5.7%), Gr 3/4 anemia (37.3, 21.1%), fever/infection with Gr 4 neutropenia (3.9, 8.9%), sepsis (4.2, 2.1%). Nonhematologic toxicity: Gr 3 nausea (3.9, 7.3%) Gr 3/4 vomiting (4.5, 9.4%), Gr 3/4 diarrhea (5.8, 2.3%) Gr 3/4 anorexia (3.7, 0.5%). Conclusions: This is one of the largest studies conducted in ED-SCLC. TC and PE show comparable activity and tolerability in the therapy-naïve setting. TC vs PE: Efficacy results TC (95% CI) n=389 PE (95% CI) n=395 Hazards Ratio (95% CI) Log-rank P value Median survival (wks) 39.3 (37.4,42.4) 40.3 (37.1,43.6) Overall survival 1.06 (0.91,1.24) P=0.4734 1-yr survival (%) 31.4 (26.7,37.0) 31.4 (26.8,30.0) Median time to progression (wks) 24.1 (22.1,25.7) 25.1 (24.1,26.9) Time to progression 1.19 (1.03,1.38) P=0.02 Complete response/partial response 25/220 21/251 Overall response rate (%) 63.0 (58.2,67.8) 68.9 (64.3,73.4) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline