title: A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: the NVALT-10 study.
abstract: BACKGROUND
  Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect.
  
  
  METHODS
  A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS).
  
  
  RESULTS
  Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% confidence interval (CI) 0.58-1.02; P = 0.06], for overall survival (OS) 0.67 (95% CI 0.49-0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively.
  
  
  CONCLUSIONS
  PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology.
  
  
  BACKGROUND
  NCT00835471.
authors.affiliation: Department of Pulmonary Diseases, Amphia Hospital, Breda.
authors.forename: J G
authors.initials: JG
authors.lastname: Aerts
authors.forename: H
authors.initials: H
authors.lastname: Codrington
authors.forename: N A G
authors.initials: NA
authors.lastname: Lankheet
authors.forename: S
authors.initials: S
authors.lastname: Burgers
authors.forename: B
authors.initials: B
authors.lastname: Biesma
authors.forename: A-M C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: A D
authors.initials: AD
authors.lastname: Vincent
authors.forename: O
authors.initials: O
authors.lastname: Dalesio
authors.forename: H J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: E F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011799:Quinazolines / Q000008:administration & dosage*; D012008:Recurrence; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D005971:Glutamates; D011799:Quinazolines; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine; D000069347:Erlotinib Hydrochloride
keywords: NSCLC; erlotinib; intercalated; second line