Cabazitaxel (Cbz) versus topotecan in patients (pts) with small cell lung cancer (SCLC) that has progressed during or after first-line treatment with platinum-based chemotherapy: A randomized phase II study.

TPS7609 Background: Approximately 12–15% of pts with lung cancer have SCLC. Although first-line platinum-based chemotherapy regimens may be effective, pts often experience rapid relapse and develop systemic metastases. Median survival after SCLC relapse varies from 13 to 35 weeks. As such, there is a substantial unmet need for more effective second-line treatments. Clinical studies suggest that taxanes are effective in relapsed SCLC, and Cbz, a next-generation taxane, has shown efficacy in the second-line treatment of taxane-resistant tumors (de Bono JS, et al. Lancet 2010;376: 1147–54; Pivot X, et al. Ann Oncol 2008;19:1547–52). Assessment of Cbz treatment for SCLC is therefore warranted. Methods: This is a multinational, open-label Phase II study (NCT01500720) in pts with confirmed, measurable, locally advanced or metastatic SCLC whose disease has progressed during/after first-line platinum-based chemotherapy. Pts aged ≥ 18 years with ECOG performance status ≤ 1 are eligible, but those with > 1 prior chemotherapy regimen or prior topotecan or taxane use are excluded. Pts are randomized 1:1 to receive IV Cbz 25 mg/m2 (Day 1 Q3W) or IV topotecan 1.5 mg/m2 (Days 1–5 Q3W). Pts are divided into chemo-sensitive and chemo-refractory subgroups, while stratification is based on the presence of brain metastases (yes vs no) and by lactate dehydrogenase plasma concentration (≤ or > upper limit). Pts will be treated until disease progression, unacceptable toxicity or withdrawal of consent. The primary objective is assessment of progression-free survival (PFS). Secondary objectives include assessment of other efficacy endpoints (proportion of pts free of disease progression at 12 weeks, tumor response and overall survival), safety and health-related quality of life. A centralized imaging review process is being used to independently review tumor measurements. Planned enrollment is 172 pts (to provide 80% power for PFS analysis). The first pt was enrolled in March 2012. By December 2012, 91 pts had been randomized in 38 sites. Clinical trial information: NCT01500720.