title: Phase II study of everolimus-erlotinib in previously treated patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Preclinical data suggest combining a mammalian target of rapamycin inhibitor with erlotinib could provide synergistic antitumor effects in advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  In this multicenter, open-label, phase II study, patients with advanced NSCLC that progressed after one to two previous chemotherapy regimens were randomized 1:1 to erlotinib 150 mg/day±everolimus 5 mg/day. Primary end point was the disease control rate (DCR) at 3 months; secondary end points included progression-free survival (PFS) and safety.
  
  
  RESULTS
  One hundred thirty-three patients received everolimus-erlotinib (n=66) or erlotinib alone (n=67). The DCR at 3 months was 39.4% and 28.4%, respectively. The probability for the difference in disease control at 3 months to be ≥15% was estimated to be 29.8%, which was below the prespecified probability threshold of ≥40%. Median PFS was 2.9 and 2.0 months, respectively. Grade 3/4 adverse events occurred in 72.7% and 32.3% of patients, respectively. Grade 3/4 stomatitis was observed in 31.8% of combination therapy recipients.
  
  
  CONCLUSIONS
  Everolimus 5 mg/day plus erlotinib 150 mg/day was not considered sufficiently efficacious per the predefined study criteria. The combination does not warrant further investigation based on increased toxicity and the lack of substantial improvement in disease stabilization.
authors.affiliation: Department of Cancer Medicine/Thoracic Unit, Institut Gustave Roussy, Villejuif.
authors.forename: B
authors.initials: B
authors.lastname: Besse
authors.forename: N
authors.initials: N
authors.lastname: Leighl
authors.forename: J
authors.initials: J
authors.lastname: Bennouna
authors.forename: V A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.forename: N
authors.initials: N
authors.lastname: Blais
authors.forename: A M
authors.initials: AM
authors.lastname: Traynor
authors.forename: J-C
authors.initials: JC
authors.lastname: Soria
authors.forename: S
authors.initials: S
authors.lastname: Gogov
authors.forename: N
authors.initials: N
authors.lastname: Miller
authors.forename: V
authors.initials: V
authors.lastname: Jehl
authors.forename: B E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D000068338:Everolimus; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000068338:Everolimus; D000069347:Erlotinib Hydrochloride; D020123:Sirolimus
keywords: disease control rate; erlotinib; everolimus; non-small-cell lung cancer; progression-free survival; stomatitis