title: SWOG S0722: phase II study of mTOR inhibitor everolimus (RAD001) in advanced malignant pleural mesothelioma (MPM).
abstract: BACKGROUND
  The PI3K/Akt/mammalian target of rapamycin pathway is activated in a majority of malignant pleural mesotheliomas (MPM). We evaluated the activity of everolimus, an oral mammalian target of rapamycin inhibitor, in patients with unresectable MPM.
  
  
  METHODS
  MPM patients who had received at least one but no more than two prior chemotherapy regimens, which must have been platinum-based, were treated with 10 mg of everolimus daily. The primary endpoint was 4-month progression-free survival (PFS) by RECIST 1.1.
  
  
  RESULTS
  A total of 59 evaluable patients were included in the analysis. The median duration of treatment was 2 cycles (56 days). Overall response rate was 2% [95% confidence interval (CI): 0-12%] by RECIST 1.1 and 0% (0-10%) by modified RECIST for MPM. The 4-month PFS rate was 29% (95% CI: 17-41%) by RECIST 1.1, and 27% (95% CI: 16-39%) by modified RECIST. The median PFS was 2.8 months (95% CI: 1.8-3.4) by RECIST 1.1. The median overall survival was 6.3 months (95% CI: 4.0-8.0). There was no difference in PFS among patients who received one or two prior chemotherapy regimens (p = 0.74). There was no difference in overall survival between patients with epithelioid histology versus other types (p = 0.47). The most common toxicities were fatigue (59%), hypertriglyceridemia (44%), anemia (42%), oral mucositis (34%), nausea (32%), and anorexia (32%). The most common grade 3 to 4 toxicities were fatigue (10.2%), anemia (6.8%), and lung infection (6.8%).
  
  
  CONCLUSIONS
  Everolimus has limited clinical activity in advanced MPM patients. Additional studies of single-agent everolimus in advanced MPM are not warranted.
authors.affiliation: *Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA; †SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; ‡Department of Medicine, Arizona Cancer Center, University of Arizona Tucson School of Medicine, Tucson, AZ; §Department of Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA; ║Fox Chase Cancer Center, Philadelphia, PA; ¶Department of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and #Department of Medicine, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Sai-Hong Ignatius
authors.initials: SH
authors.lastname: Ou
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Linda L
authors.initials: LL
authors.lastname: Garland
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
authors.forename: Anne S
authors.initials: AS
authors.lastname: Tsao
authors.forename: Antoniette J
authors.initials: AJ
authors.lastname: Wozniak
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus