title: A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNα versus IFNα in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis.
abstract: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNα versus IFN in metastatic renal cell carcinoma (RCC).
  
  
  
  In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 μg/kg i. v. in three cycles of four once-daily injections) + IFN (9 MU s.c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS).
  
  
  
  This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E-120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile.
  
  
  
  The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup. Clin Cancer Res; 22(13); 3172-81. ©2016 AACR.
authors: The Christie NHS Foundation Trust, Manchester, United Kingdom. Robert.Hawkins@ics.manchester.ac.uk.
authors: Robert E
authors: RE
authors: Hawkins
authors: Royal Marsden Hospital NHS Trust, London, United Kingdom.
authors: Martin
authors: M
authors: Gore
authors: State Regional Treatment and Diagnostics Oncology Center, Lviv, Ukraine.
authors: Yaroslav
authors: Y
authors: Shparyk
authors: Public Clinical Treatment and Prophylaxis Institution, Donetsk, Ukraine.
authors: Vladimir
authors: V
authors: Bondar
authors: Chelyabinsk Regional Clinical Oncology Dispensary, Chelyabinsk, Russia.
authors: Oleg
authors: O
authors: Gladkov
authors: Urology Clinic General Hospital for Active Treatment "St. Anna", Varna, Bulgaria.
authors: Tosho
authors: T
authors: Ganev
authors: Fundeni Clinical Institute, Bucharest, Romania.
authors: Mihai
authors: M
authors: Harza
authors: Public Treatment and Prophylaxis Institution, Chernihiv Regional Oncology Center, Chernihiv, Ukraine.
authors: Serhii
authors: S
authors: Polenkov
authors: Municipal Institution Dnipropetrov, Dnipropetrovsk, Ukraine.
authors: Igor
authors: I
authors: Bondarenko
authors: City Clinical Oncology Dispensary, St. Petersburg, Russia.
authors: Petr
authors: P
authors: Karlov
authors: Medical Radiological Research Center, Obninsk, Russia.
authors: Oleg
authors: O
authors: Karyakin
authors: Republic Oncology Dispensary, Kazan, Russia.
authors: Rustem
authors: R
authors: Khasanov
authors: Active Biotech AB, Lund, Sweden.
authors: Gunnar
authors: G
authors: Hedlund
authors: Active Biotech AB, Lund, Sweden.
authors: Goran
authors: G
authors: Forsberg
authors: Active Biotech AB, Lund, Sweden.
authors: Örjan
authors: Ö
authors: Nordle
authors: Cambridge University Health Partners, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Timothy
authors: T
authors: Eisen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004768:Enterotoxins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015415:Biomarkers; D004768:Enterotoxins; C508600:IL6 protein, human; D018796:Immunoconjugates; D016898:Interferon-alpha; D015850:Interleukin-6; C479099:enterotoxin A E-120, Staphylococcal; C543500:naptumomab estafenatox