• Respiratory Cancers
• Cancer Clinical Trials

• Respiratory Cancers
• Cancer
• Oncology Clinical Trials
• Oncology

A randomized, open-label Phase 2 trial with patients who had small cell lung cancer (SCLC) that had progressed during or after first-line platinum-based chemotherapy found no significant difference in progression-free survival (PFS) with cabazitaxel against topotecan, the current standard for comparison [Riemsma R et al. BMC Cancer 2010]. The median overall survival (OS) was shorter for patients taking cabazitaxel versus those taking topotecan [NCT01500720].

The authors of the study sought to determine the efficacy of cabazitaxel, a next-generation taxane shown to be safe and effective as second-line treatment of metastatic castrate-resistant prostate cancer (mCRPC) and other advanced solid tumors [de Bono JS et al. Lancet 2010; Dieras V et al. Eur J Cancer 2013; Fumoleau P et al. BMC Cancer 2013; Pivot X et al. Ann Oncol 2008] versus topotecan as second-line treatment of SCLC. Two randomized studies demonstrated the efficacy of topotecan in relapsed SCLC [Ardizzoni A et al. J Clin Oncol 1997; von Pawel I et al. J Clin Oncol 1999]. No other agent has shown superior clinical activity.

One hundred seventy-nine patients with locally advanced or metastatic SCLC were randomly assigned to intravenous (IV) cabazitaxel 25 mg/m² (Day 1 every 3 weeks; n=91) or IV topotecan 1.5 mg/m² (Days 1 to 5, every 3 weeks; n=88). The patients were divided into 2 subgroups: chemosensitive (progression ≥90 days; n=91) or chemorefractory (progression during or within 90 days; n=88). They were also separated by the presence or the absence of brain metastasis and by plasma concentration of lactate dehydrogenase (LDH; less than or equal to vs greater than the upper limit of normal).

Key eligibility criteria included Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1, 1 round of prior chemotherapy, and no prior treatment with a taxane or with topotecan.

Tracey L. Evans, MD, Abramson Cancer Center, Philadelphia, PA, USA, presented results for the primary endpoint of improvement in PFS and the secondary endpoints of OS, tumor response rate, and adverse events from this multinational trial. Other secondary endpoints are disease progression-free rate at 12 weeks, duration of response, and health-related quality of life (HRQoL).

The median age of the patients was 61 years. Baseline characteristics were balanced between treatment arms; approximately 50% of patients in each arm were chemorefractory. Patients received a median number of 2 cycles of cabazitaxel and 4 cycles of topotecan.

Median PFS was 1.4 months with cabazitaxel and 3.0 months with topotecan in the intention-to-treat (ITT) analysis. The study failed to meet the primary endpoint of improvement in PFS with cabazitaxel versus topotecan (log-rank test 2-sided, p<0.0001); hazard ratio (HR), 2.169; 95% CI, 1.563 to 3.010). The median PFS was similar to the overall results in the chemosensitive (1.5 vs 3.8 months) and chemoresistant (1.4 vs 2.7 months) subgroups. The tumor response rates by ITT analysis for the overall study population and for the 2 subgroups are detailed in Table 1.

The OS was 5.2 months with cabazitaxel and 6.8 months with topotecan in the ITT population (log-rank test 2-sided, p=0.0125; HR, 1.57; 95% CI, 1.10 to 2.25). Similar results were seen for OS with the subgroups (6.3 vs 7.2 months chemosensitive; 3.4 vs 5.7 months chemorefractory).

Treatment-emergent adverse events (TEAEs) were more frequent with topotecan. Any TEAE of any grade occurred in 94.3% of the topotecan and 88.8% of the cabazitaxel groups, and ≥grade 3 TEAE occurred in 71.6% and 58.4%, respectively. Overall, 29 deaths resulted from TEAEs. TEAEs that led to death and were considered possibly related to treatment were neutropenic infection in 3 patients, febrile neutropenia in 2 patients, neutropenic sepsis in 1 patient, and cardiopulmonary failure in 1 patient.

• © 2014 MD Conference Express®