67O - Cabazitaxel (cbz) vs topotecan (tpt) in patients (pts) with small cell lung cancer (SCLC) with progressive disease during/after first-line (1l) trea...
|Date||28 March 2014|
|Session||Proffered papers 4 - SCLC and locally advanced NSCLC|
|Topics|| Anti-Cancer Agents & Biologic Therapy
Small-Cell Lung Cancer
|Citation||Journal of Thoracic Oncology (2014) 9 (Supplement 9): S7-S52. 10.1097/JTO.0000000000000131|
T. Evans1, B.C. Cho2, K. Udud3, J.R. Fischer4, F.A. Shepherd5, P. Martinez6, R. Ramlau7, K.N. Syrigos8, M. Chadjaa9, M. Wolf10
Platinum-based ctx is the 1L standard of care for SCLC, but despite high response rates, most SCLC pts experience rapid relapse and die from systemic metastases (mets). Therefore, more effective second-line (2L) treatments are needed. Taxanes are active 2L in SCLC, and Cbz is effective in 2L in other solid tumors. We compared Cbz vs Tpt in a randomized open-label Phase II trial in pts with SCLC who had progressed during/after 1L ctx (NCT01500720).
Pts with locally advanced or metastatic SCLC who had progressed during/after 1L platinum-based ctx, ECOG PS ≤1, ≤1 prior ctx and no prior taxane/Tpt treatment were enrolled. Pts received IV Cbz 25 mg/m2 (Day 1 Q3W) or IV Tpt 1.5 mg/m2 (Days 1–5 Q3W) (1:1 ratio). Pts were split into ctx-sensitive and ctx-refractory subgroups and stratified by brain mets (yes vs no) and lactate dehydrogenase (LDH) plasma concentration (≤ vs > upper limit of normal). Endpoints included progression-free survival (PFS; primary endpoint), overall survival (OS), safety and health-related quality of life.
179 pts (Cbz 90; Tpt 89) were randomized. Median age was 61 yrs. Baseline characteristics were balanced between treatment arms; approximately 50% of pts in each arm were ctx-refractory. Median number of cycles received was 2 (Cbz) and 4 (Tpt). Median PFS was 1.4 months (mo) (Cbz) and 3.0 mo (Tpt). The primary endpoint of improvement in PFS for Cbz vs Tpt was not met (log-rank test, 2-sided p<0.0001; HR=2.169, 95% CI 1.563, 3.010, 90% CI 1.648, 2.856). Similar results were observed in the ctx-sensitive and ctx-refractory subgroups. Cbz was less favorable than Tpt for OS (median: 5.2 mo Cbz, 6.8 mo Tpt; log rank test, 2-sided p=0.0125; HR=1.574, 95% CI 1.099, 2.253, 90% CI 1.165, 2.127). All-grade adverse events (AEs) were more frequent with Tpt (94.3%) vs Cbz (88.8%), as were grade 3–4 AEs (Tpt 71.6%, Cbz 58.4%). Febrile neutropenia (Tpt 15.9%, Cbz 11.2%), neutropenic infection (Tpt 6.8%, Cbz 4.5%) and neutropenic sepsis (Tpt 1.1%, Cbz 3.4%) were similar across arms.
Cbz failed to meet the primary endpoint of superior PFS and showed less favorable median OS vs Tpt in pts with SCLC who had progressed during/after 1L ctx. No new safety concerns were identified.
T. Evans: Receipt of honoraria or consultation fees:Lilly, Genentech. Husband on speakers bureau for Genentech B.C. Cho: Receipt of grants/research supports: Novartis Receipt of honoraria or consultation fees: Novartis, AstraZeneca and GSK M. Chadjaa: I am a stock shareholder and a Sanofi employee All other authors have declared no conflicts of interest.