title: Phase I/II study of tecemotide as immunotherapy in Japanese patients with unresectable stage III non-small cell lung cancer.
abstract: Unresectable stage III NSCLC (non-small cell lung cancer) confers a poor prognosis and interest is growing in the use of immunotherapy to improve outcomes for patients with this disease. We investigated the safety and efficacy of maintenance tecemotide, a mucin 1 (MUC1)-specific agent that induces T-cell responses to MUC1, versus placebo in Japanese patients with stage III unresectable NSCLC and no disease progression after primary chemoradiotherapy.
  
  
  
  Patients aged ≥20 years with unresectable stage III NSCLC, stable disease or clinical response after primary chemoradiotherapy and performance status ≤1, were recruited across 25 centers in Japan. Patients were randomized 2:1 to tecemotide (930μg as lipopeptide) or placebo subcutaneously once weekly for 8 weeks, then every 6 weeks until disease progression or treatment withdrawal. Cyclophosphamide 300mg/m2(maximum dose 600mg) was given intravenously 3days before the first dose of tecemotide. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, time to progression, time to treatment failure and safety.
  
  
  
  The intent-to-treat population comprised 172 patients; 114 received tecemotide and 58 placebo. Baseline characteristics were comparable between treatment arms. Most patients (94%) received primary concurrent chemoradiotherapy. There was no apparent trend toward increased OS time with tecemotide over placebo (median 32.4 versus 32.2 months, hazard ratio 0.95, 95% confidence interval 0.61-1.48; P=0.83). No improvements in secondary efficacy endpoints were observed. The frequency of treatment-related adverse events was similar, and serious adverse event rates were the same in both arms. There were no new safety signals.
  
  
  
  These results do not support those from a randomized phase III study (START) of improved OS with tecemotide in the subgroup of patients treated with primary concurrent chemoradiotherapy.
authors.affiliation: Institute of Biomedical Research and Innovation, 2-2 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: katakami@fbri.org.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.affiliation: Aichi Cancer Center Central Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. Electronic address: 107974@aichi-cc.jp.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: hnokihar@ncc.go.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan. Electronic address: imamura-fu@mc.pref.osaka.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Imamura
authors.affiliation: Saitama Cancer Center, 780 Komuro, Inamachi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: hiroshi_sakai@cancer-c.pref.saitama.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka 591-8555, Japan. Electronic address: s-atagi@kch.hosp.go.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Atagi
authors.affiliation: Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: mnishio@jfcr.or.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
authors.affiliation: Toyama University Hospital, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: tkashii@med.u-toyama.ac.jp.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kashii
authors.affiliation: Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi, Hyogo 673-8558, Japan. Electronic address: satouchi@hp.pref.hyogo.jp.
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.affiliation: Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt D135/003, Germany. Electronic address: christoph.helwig@merckgroup.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: Helwig
authors.affiliation: Merck Serono Co. Ltd., Arco Tower 4F, 8-1 Shimomeguro 1-chome, Meguro-ku 153-8926, Tokyo, Japan. Electronic address: morihiro.watanabe@merckgroup.com.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan. Electronic address: tamuratomohide@gmail.com.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; C518273:L-BLP25; D008562:Membrane Glycoproteins; D003520:Cyclophosphamide
keywords: Immunotherapy; MUC1; Non-small cell lung cancer; Primary chemoradiotherapy; Tecemotide