Oncology
Prostate Cancer
Gene Signature Predicts Survival Benefits With Immunotherapy for mCRPC
Overview
Clinical Study Title:
Blood-Based Predictive Biomarkers for Overall Survival in Patients Receiving the Immunotherapy Sipuleucel-T
Clinical Study Abstract:
Sipuleucel-T is an autologous immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Optimal sequencing of the many recently approved drug therapies for mCRPC and optimal patient selection for sipuleucel-T are both areas of active investigation. Sipuleucel-T is derived from the patient’s peripheral blood mononuclear cells, once cultured and activated, ex vivo. Gene expression signatures in the peripheral blood mononuclear cells (PBMCs) correlate with prognosis in mCRPC, and therefore such signatures may help predict benefit with sipuleucel-T. The present study used PBMCs from patients in the IMPACT (Identification of Men with a Genetic Predisposition to Prostate Cancer) trial to investigate gene expression that might be predictive of overall survival (OS).
Of the 50 top candidate genes, a total of 5 were found to be associated with OS. High expression of SNTB1 and CHI3L2 and low expression of SYNGR3, AURKC, and ZNF268 were associated with improved OS in sipuleucel-T–treated patients, but not in control arm patients. Investigators used a composite score based on genetic expression and applied it to patients treated with sipuleucel-T. OS in the top and middle sipuleucel-T tertiles was significantly better compared with the corresponding control groups, while the lowest tertile of sipuleucel-T–treated patients had a median OS similar to that of the control arm. Investigators concluded that such a gene expression-based scoring system at baseline might help predict OS outcomes for sipuleucel-T–treated patients.
Reference:
Oh WK, Kandadi H, Sheikh NA, et al. Blood-based predictive biomarkers for overall survival in patients receiving the immunotherapy sipuleucel-T. J Clin Oncol. 2017;35(suppl 7S):Abstract 36.
Expert Commentary
William K. Oh, MD
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Predictive biomarkers are the holy grail of all cancer therapies, as they allow “precision medicine” – a highly overused term. The use of molecular signatures as prognostic biomarkers is well established. There are also some molecular genetic tests that can influence the decision to use a specific therapy. The best example of this latter case is the Oncotype Dx test in breast cancer, which may lead to the use of adjuvant chemotherapy. However, the use of a specific molecular test to determine whether a patient should or should not receive a drug remains relatively uncommon. An example of this is the use of cetuximab in metastatic colorectal cancer in patients with wild-type KRAS and mutations in epidermal growth factor receptor. |
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“My collaborators and I sought to determine whether a blood-based RNA signature could predict survival benefit from sipuleucel-T in men with mCRPC.”
In the present study, my collaborators and I sought to determine whether a blood-based RNA signature could predict survival benefit from sipuleucel-T in men with mCRPC. We developed a 5-gene signature that distinguished the top 2 tertiles of survival in sipuleucel-T–treated but not control-treated patients. In the lowest tertile expressing this signature, there was no difference in survival compared with controls. Indeed, this signature was no different from the control group in terms of outcome. This suggests that a 5-gene molecular signature could distinguish a group more likely to benefit from sipuleucel-T, a finding that could direct more specific populations to this treatment.
