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Avelumab in Men With Metastatic Castration-Resistant Prostate Cancer, Enriched for Patients Treated Previously With a

Ravi A Madan1, Jason M Redman1,2, Fatima Karzai1

  • 1Genitourinary Malignancies Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Journal of Immunotherapy (Hagerstown, Md. : 1997)
|February 23, 2023
PubMed

Insights

Sequential therapy with avelumab after prostate cancer vaccines did not improve T-cell responses or clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). This suggests programmed death ligand-1 inhibition may not benefit patients previously treated with therapeutic cancer vaccines.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Vaccines

Background:

  • Therapeutic cancer vaccines, like sipuleucel-T for prostate cancer, can yield clinical benefits by eliciting immune responses.
  • The impact of sequential checkpoint inhibitors following therapeutic cancer vaccines on immune responses remains unclear.
  • Avelumab, an anti-programmed death ligand-1 antibody, was evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients, including those with prior vaccine therapy.

Purpose of the Study:

  • To investigate the effects of sequential programmed death ligand-1 inhibition (avelumab) after therapeutic cancer vaccine treatment in patients with mCRPC.
  • To assess changes in antigen-specific T-cell responses following avelumab treatment in this patient population.

Main Methods:

  • An open-label, phase 1 trial expansion cohort evaluated mCRPC patients receiving intravenous avelumab.
  • Peripheral blood T-cell responses to prostatic acid phosphatase (PAP) and PA2024 peptide were measured pre- and post-treatment.
  • Safety, prostate-specific antigen (PSA) levels, and objective response by RECIST criteria were assessed.

Main Results:

  • Avelumab demonstrated a manageable safety profile.
  • No sustained PSA decreases were observed, and limited objective responses were noted.
  • Analysis of antigen-specific T-cell responses did not reveal significant changes in interferon-γ production or proliferation.
  • A high proportion of patients (79%) who received prior vaccine therapy achieved stable disease (SD).

Conclusions:

  • Sequential therapy with avelumab after therapeutic cancer vaccines did not enhance antigen-specific T-cell responses in mCRPC patients.
  • The study does not support the use of programmed death ligand-1 inhibition following therapeutic cancer vaccine therapy in mCRPC.
  • Further research is needed to understand optimal sequencing strategies for cancer vaccines and checkpoint inhibitors.

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