Introduction: Patients with small-cell lung cancer (SCLC) typically respond well to initial chemotherapy. However, relapse invariably occurs, and topotecan, the only approved second-line treatment option, has limited efficacy. Taxanes have activity in SCLC, and cabazitaxel is a second-generation taxane with potential for enhanced activity in chemorefractory malignancies. Methods: Patients with SCLC who relapsed after initial platinum-based chemotherapy were randomly assigned to receive cabazitaxel 25 mg/m2 every 21 days or topotecan 1.5 mg/m2 on days 1-5 every 21 days. Two patient subgroups, defined by chemosensitive and chemo-resistant/ refractory disease, were assessed in combination and separately. Results: The safety profile of cabazitaxel and topotecan was consistent with previous studies, and despite considerable toxicity in both arms, no new safety concerns were identified. Patients receiving cabazitaxel had inferior progression-free survival compared with topotecan (1.4 versus 3.0 months, respectively; two-sided p < 0.0001; hazard ratio = 2.17, 95% confidence interval = 1.563-3.010), and results were similar in both the chemosensitive and chemorefractory subgroups. No complete responses were observed in either arm, and no partial responses were observed in the cabazitaxel group. The partial response rate in the topotecan arm was 10%. Median overall survival was 5.2 months in the cabazitaxel arm and 6.8 months in the topotecan arm (two-sided p = 0.0125; hazard ratio = 1.57, 95% confidence interval = 1.10-2.25). Conclusion: Cabazitaxel, a next-generation taxane, had inferior efficacy when compared with standard-dose topotecan in the treatment of relapsed SCLC. Topotecan remains a suboptimal therapy, and continued efforts to develop improved second-line treatments are warranted.
Bibliographical noteFunding Information:
Disclosure: This study was funded by Sanofi. TE has received teaching honoraria from Celgene, and reimbursement for travel to an investigator meeting organized by Celgene. TE has also provided manuscript writing assistance at Celgene, has an ongoing consultancy role at Genentech and Eli Lilly, is a member of the ABIM SEP committee, has created exam questions for SEP oncology, and is a member of the ASCO quality care committee and chairs the measures sub-committee. BCC was a board member at Boehringer Ingelheim and Novartis, has grants pending at Boehringer Ingelheim, Novartis, AstraZeneca and Bayer, and has received payment for lectures at Novartis. FS had a consultancy role at Sanofi Aventis. RR has received support for travel to meetings from Merck KGaA, and payment for lectures/speaker bureaus from Eli Lilly, Boeringer Ingelheim and MSD. KS has received consultancy fees/honorarium from Merck Serono and Boehringer Ingelheim. LS and MC are employees of, and hold stock at, Sanofi. KU, JF, PM and MW have nothing to disclose. The authors received support in the form of medical writing services from Paul Scutt of MediTech Media, funded by Sanofi.
Copyright © 2015 by the International Association for the Study of Lung Cancer.
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine