title: Cabazitaxel Versus Topotecan in Patients with Small-Cell Lung Cancer with Progressive Disease During or After First-Line Platinum-Based Chemotherapy.
abstract: BACKGROUND
  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/m every 21 days or topotecan 1.5 mg/m 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Perelman Center for Advanced Medicine, Philadelphia, Pennsylvania; †Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea; ‡Korányi National Institute of Pulmonology, Budapest, Hungary; §Klinikum Loewenstein, Loewenstein, Germany; ‖Princess Margaret Cancer Centre, Toronto, Ontario, Canada; ¶Vall d'Hebron Institute of Oncology, Barcelona, Spain; #Oncology Department, Poznan University of Medical Sciences, Poznan, Poland; **Oncology Unit, 3rd Department of Medicine, Athens University School of Medicine, Sotiria General Hospital, Athens, Greece; ††Sanofi, Bridgewater, New Jersey; ‡‡Sanofi, Vitry-sur-Seine, France; and §§Division of Haematology and Oncology, Klinikum Kassel, Kassel, Germany.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Evans
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
authors.forename: Katalin
authors.initials: K
authors.lastname: Udud
authors.forename: Juergen R
authors.initials: JR
authors.lastname: Fischer
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Syrigos
authors.forename: Liji
authors.initials: L
authors.lastname: Shen
authors.forename: Mustapha
authors.initials: M
authors.lastname: Chadjaa
authors.forename: Martin
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use; D066066:Response Evaluation Criteria in Solid Tumors; D019233:Retreatment; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D015996:Survival Rate; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; D043823:Taxoids; C552428:cabazitaxel; D019772:Topotecan