title: Relevance of platinum-sensitivity status in relapsed/refractory extensive-stage small-cell lung cancer in the modern era: a patient-level analysis of southwest oncology group trials.
abstract: BACKGROUND
  Extensive-stage small-cell lung cancer (SCLC) patients who progress after platinum-based chemotherapy are traditionally categorized as platinum sensitive (progression ≥ 90 days from last platinum dose) or refractory (progression < 90 days), a practice arising from seminal observations of worse survival in refractory patients. Subsequent trials accounted for platinum sensitivity, resulting in higher sample sizes and increased resource use.
  
  
  METHODS
  To assess whether platinum-sensitivity status remains associated with outcomes, patient-level data from recent Southwest Oncology Group trials in second- and/or third-line extensive-stage SCLC were pooled. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) accounting for platinum sensitivity were calculated using unadjusted and adjusted Cox Proportional Hazard models. Recursive partitioning was performed to define prognostic risk groups.
  
  
  RESULTS
  Of 329 patients, 151 were platinum sensitive and 178 refractory. HRs from unadjusted Cox PFS and OS models for refractory versus sensitive disease were 1.0 (95% confidence interval, 0.81-1.25; p = 0.98) and 1.24 (0.99-1.57; p = 0.06), respectively. Adjusted Cox models showed that only elevated serum lactate dehydrogenase (HR, 2.04; p < 0.001), males (HR, 1.36; p = 0.04), performance status of 1 (HR, 1.25; p = 0.02), and weight loss greater than or equal to 5% (1.53, p = 0.01) were independently associated with OS. Platinum-sensitivity status was not associated with PFS (HR, 1.11; p = 0.49) or OS (HR, 1.25; p = 0.14), except in a model that excluded 36 patients who received more than one prior chemotherapy regimen (HR, 1.34; p = 0.049). Prognostic groups with differential OS outcomes (high, intermediate, and poor risk) were identified.
  
  
  CONCLUSIONS
  Platinum-sensitivity status may no longer be strongly associated with PFS or OS in at least one multivariate model. Validation of prognostic risk groups identified here is warranted. These data have critical implications in the design of future SCLC trials.
authors.affiliation: *University of California Davis Comprehensive Cancer Center, Sacramento, California; †SWOG Statistical Center and the Fred Hutchinson Cancer Research Center, Seattle, Washington; ‡Humboldt Medical Specialists, Eureka, California; and §Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Semrad
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Allen
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Gitlitz
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012008:Recurrence; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000077157:Sorafenib; D019772:Topotecan / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001897:Boronic Acids; D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D011719:Pyrazines; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D009536:Niacinamide; D000069286:Bortezomib; D019772:Topotecan; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor