title: Telomerase peptide vaccination in NSCLC: a phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial.
abstract: OBJECTIVE
  We report two clinical trials in non-small cell lung cancer (NSCLC) patients evaluating immune response, toxicity, and clinical outcome after vaccination with the telomerase peptide GV1001: a phase II trial (CTN-2006) in patients vaccinated after chemoradiotherapy and an 8-year update on a previously reported phase I/II trial (CTN-2000).
  
  
  METHODS
  CTN-2006: 23 inoperable stage III patients received radiotherapy (2 Gy × 30) and weekly docetaxel (20 mg/m(2)), followed by GV1001 vaccination. CTN-2000: 26 patients were vaccinated with two telomerase peptides (GV1001 and I540). The immune responses were evaluated by T-cell proliferation and cytokine assays.
  
  
  RESULTS
  CTN-2006 trial: a GV1001-specific immune response developed in 16/20 evaluable patients. Long-term immunomonitoring showed persisting responses in 13 subjects. Serious adverse events were not observed. Immune responders recorded a median PFS of 371 days, compared with 182 days for nonresponders (P = 0.20). CTN-2000 trial update: 13/24 evaluable subjects developed a GV1001 response. The immune responders achieved increased survival compared with nonresponders (median 19 months vs. 3.5 months; P < 0.001). Follow-up of four long-time survivors showed that they all harbored durable GV1001-specific T-cell memory responses and IFNγ(high)/IL-10(low)/IL-4(low) cytokine profiles. Two patients are free of disease after 108 and 93 months, respectively.
  
  
  CONCLUSIONS
  Vaccination with GV1001 is well tolerated, immunizes the majority of NSCLC patients and establishes durable T-cell memory. The considerable immune response rate and low toxicity in the phase II trial support the concept of combining chemoradiotherapy with vaccination. The survival advantage observed for immune responders warrants a randomized trial.
authors.affiliation: Department of Clinical Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
authors.forename: Paal Fr
authors.initials: PF
authors.lastname: Brunsvig
authors.forename: Jon Amund
authors.initials: JA
authors.lastname: Kyte
authors.forename: Christian
authors.initials: C
authors.lastname: Kersten
authors.forename: Stein
authors.initials: S
authors.lastname: Sundstrøm
authors.forename: Mona
authors.initials: M
authors.lastname: Møller
authors.forename: Marta
authors.initials: M
authors.lastname: Nyakas
authors.forename: Gaute L
authors.initials: GL
authors.lastname: Hansen
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010349:Patient Compliance; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D019098:Telomerase / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D010446:Peptide Fragments; D043823:Taxoids; D000077143:Docetaxel; C514987:GV1001 peptide; D019098:Telomerase