Combining Radiation Therapy with Immunotherapy in Metastatic Castration-Resistant Prostate Cancer - Expert Commentary

Immune checkpoint blockade (ICB) demonstrated modest clinical activity in patients with metastatic castration-resistant prostate cancer (CRPC). However, it is unclear if radiation therapy synergizes with ICB to enhance the antitumor immune response.


A recently published phase II study by Kwan et al. in European Urology investigated the efficacy of avelumab with stereotactic ablative body radiotherapy (SABR) in patients with mCRPC. The study recruited 31 patients with heavily pretreated mCRPC. Patients received avelumab every two weeks and a single fraction of SABR (20 Gy) to one or two disease sites before the first and the second doses of avelumab. The primary endpoint was disease control rate (DCR). The median follow-up was 18 months.

The study met its primary endpoint with a DCR of 48% (15/31). In 16 patients with measurable disease, five (30%) patients achieved a partial response. The site of SABR administration or the number of irradiated metastatic sites did not impact the outcomes. The median radiologic progression-free and overall survivals were 8.4 and 14.1 months, respectively. Six patients experienced grade 3/4 treatment-related adverse events.

Detectable circulating tumor DNA (ctDNA) at baseline was not associated with DCR. In one patient, a reduction in ctDNA fraction and TP53 allele frequency preceded the radiologic response. The combined radioimmunotherapy showed promising results without additional safety concerns. Further head-to-head comparisons of single versus combined treatment modalities are still needed to validate the efficacy and safety of this approach.


Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

References:

  1. Kwan EM, Spain L, Anton A, Gan CL, Garrett L, Chang D, et al. Avelumab Combined with Stereotactic Ablative Body Radiotherapy in Metastatic Castration-resistant Prostate Cancer: The Phase 2 ICE-PAC Clinical Trial. Eur Urol. 2021. Doi. 10.1016/j.eururo.2021.08.011
  2. Antonarakis ES, Piulats JM, Gross-Goupil M, Goh J, Ojamaa K, Hoimes CJ, et al. Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. J Clin Oncol. 2020 Feb 10;38(5):395–405.

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