Topotecan/cisplatin (TP) compared to cisplatin/etoposide (PE) for patients with extensive disease-small cell lung cancer (ED- SCLC): Final results of a randomised phase III trial

Abstract

7513 Background: This phase III study was conducted to evaluate the efficacy and safety of TP compared to the standard first- line regimen PE. Methods: Chemotherapy-naïve patients with confirmed ED-SCLC and ECOG performance status ≤ 2 were randomised to receive topotecan (1mg/m2 i.v., d1–5)/cisplatin (75 mg/m2 i.v., d5) or etoposide (100mg/m2 i.v., d1–3)/cisplatin (75 mg/m2 i.v., d1) for a maximum of 6 cycles, q 21 d. Primary objective was to show superiority in OS of TP compared to PE using a two sided log-rank test with a 5% type I error and 80% power. If superiority was not shown, a non-inferiority test was pre-specified (non-inferiority threshold was 10 percentage points relative to the median survival time in the standard arm). Secondary endpoints were 1 year survival rate, objective response rate, time to progression and safety. Results: 795 patients were recruited (358 TP, 345 PE, 92 TE) in 84 centres in Germany and Austria. Baseline characteristics were balanced. Median number of cycles was 6, both for TP and PE. A third study arm topotecan (1mg/m2 i.v., d1–5)/etoposide (80–100 mg/m2 i.v., d3–5) was abandoned in April 2004 following a recommendation of an IDSMB due to an increased number of treatment related deaths. Haematologic toxicity: TP vs. PE: G3/4 neutropenia (35.7/ 35.8%), Gr 3/4 thrombocytopenia (18.7/4.8%), Gr 3/4 anaemia (11.6/6.7%), febrile neutropenia (2.0/2.7%), sepsis (1.7/1.2%), toxicity related deaths (5.2/2.7%). Transfusions of red-cell units (420/153). Non-haematological toxicity was comparable. Conclusion: Topotecan/cisplatin (TP) is non inferior to cisplatin/etoposide (PE) in OS and is superior in TTP and ORR. TP may be considered as an alternative 1st line treatment option for patients with ED-SCLC. TP PE p- value Median survival (months) 99% CI-PP analysis 10.3 9.3–11.3 9.4 8.2–10.9 0.40 1- year survival rate 95% CI 39.7% 34.5%–44.9% 36.1% 30.9%–41.4% 0.29 Median TTP (months) 95% CI 6.9 6.4–7.3 5.9 5.5–6.6 0.004 CR 95% CI 9.5% 6.7%–13.1% 6.9% 4.4%–10.2% 0.21 ORR (CR+PR) 95% CI 55.5% 50.3%–60.7% 45.5% 40.2%–50.8% 0.01 Efficacy results (ITT unless indicated) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline