Analysis of pre-treatment markers predictive of treatment benefit for the therapeutic cancer vaccine MVA-5T4 (TroVax).
Cancer vaccines such as MVA-5T4 (TroVax(®)) must induce an efficacious immune response to deliver therapeutic benefit. The identification of biomarkers that impact on the clinical and/or immunological efficacy of cancer vaccines is required in order to select patients who are most likely to benefit from this treatment modality. Here, we sought to identify a predictor of treatment benefit for renal cancer patients treated with MVA-5T4. Statistical modeling was undertaken using data from a phase III trial in which patients requiring first-line treatment for metastatic renal cell carcinoma were randomized 1:1 to receive MVA-5T4 or placebo alongside sunitinib, IL-2 or IFN-α. Numerous pre-treatment factors associated with inflammatory anemia (e.g., CRP, hemoglobin, hematocrit, IL-6, ferritin, platelets) demonstrated a significant relationship with tumor burden and patient survival. From these prognostic factors, the pre-treatment mean corpuscular hemoglobin concentration (MCHC) was found to be the best predictor of treatment benefit (P < 0.01) for MVA-5T4 treated patients and also correlated positively with tumor shrinkage (P < 0.001). Furthermore, MCHC levels showed a significant positive association with 5T4 antibody response (P = 0.01). The latter result was confirmed using an independent data set comprising phase II trials of MVA-5T4 in patients with colorectal, renal and prostate cancers. Retrospective analyses demonstrated that RCC patients who had very large tumor burdens and low MCHC levels received little or no benefit from treatment with MVA-5T4; however, patients with smaller tumor burdens and normal MCHC levels received substantial benefit from treatment with MVA-5T4.
Oxford BioMedica (UK) Ltd, The Medawar Centre, Oxford Science Park, Oxford, OX4 4GA, UK. r.harrop@oxfordbiomedica.co.uk
Richard
R
Harrop
Peter
P
Treasure
Jackie
J
de Belin
Michelle
M
Kelleher
Gemma
G
Bolton
Stuart
S
Naylor
William H
WH
Shingler
D000740:Anemia / Q000276:immunology / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006454:Hemoglobins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D019444:Vaccines, DNA
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D006454:Hemoglobins; D016898:Interferon-alpha; D007376:Interleukin-2; C504058:TroVax; D019444:Vaccines, DNA