title: A randomized phase II study of LY2510924 and carboplatin/etoposide versus carboplatin/etoposide in extensive-disease small cell lung cancer.
abstract: This multicenter, open-label, randomized phase II study evaluated the efficacy and safety of LY2510924 (LY) added to first-line standard of care (SOC) chemotherapy for extensive-disease small cell lung cancer (ED-SCLC) and explored the predictive value of C-X-C motif receptor 4 (CXCR4) tumor response.
  
  
  
  Patients with treatment-naïve ED-SCLC were randomized (1:1) to receive up to six 21-day cycles of carboplatin/etoposide alone (SOC) or in combination with 20mg LY2510924 administered subcutaneously on days 1-7 of each cycle (LY+SOC). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and safety. Response relative to CXCR4 expression on baseline tumor was an exploratory endpoint.
  
  
  
  Of 94 patients randomized, 90 received treatment (LY+SOC, n=47; SOC, n=43). Median PFS (95% confidence interval [CI]) was 5.88 (4.83, 6.24) months for LY+SOC versus 5.85 (4.63, 5.51) months for SOC (hazard ratio [95% CI], 1.01 [0.62, 1.63]; p=0.9806). Median OS (95% CI) was 9.72 (6.64, 11.70) months for LY+SOC versus 11.14 (8.25, 13.44) months for SOC. ORR was 74.5% for LY+SOC versus 81% for SOC. Safety results between arms were similar, although the following adverse events were more frequent on the LY+SOC arm: anemia (61.7% vs 46.5%), neutropenia (61.7% vs 53.5%), leukopenia (27.7% vs 9.3%), vomiting (27.7% vs 16.3%), and pneumonia (10.6% vs 2.3%). In patients whose baseline CXCR4 expression was above the optimal cutoff (H-score 210), the hazard ratio (95% CI) was 1.27 (0.51, 3.15).
  
  
  
  LY2510924 did not improve efficacy but had an acceptable toxicity profile when added to SOC for ED-SCLC.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, United States. Electronic address: rsalgia@coh.org.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Stille
authors.affiliation: Florida Cancer Specialists, St. Petersburg, FL, United States.
authors.forename: R Waide
authors.initials: RW
authors.lastname: Weaver
authors.affiliation: Florida Cancer Specialists, Fort Myers, FL, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: McCleod
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, United States.
authors.forename: Oday
authors.initials: O
authors.lastname: Hamid
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, United States.
authors.forename: John
authors.initials: J
authors.lastname: Polzer
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roberson
authors.affiliation: PharPoint Research Inc., Durham, NC, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Flynt
authors.affiliation: Lung Cancer Research Program, Sarah Cannon Research Institute, LLC, Nashville, TN, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C000595455:LY2510924; D010456:Peptides, Cyclic; D005047:Etoposide; D016190:Carboplatin
keywords: CXCR4; Extensive-disease small cell lung cancer; LY2510924; Phase II trial