Dramatic response to combination pembrolizumab and radiation in metastatic castration resistant prostate cancer

Abstract

Immune checkpoint inhibitors targeting PD-1 and PD-L1 have demonstrated anti-tumor activity in several advanced solid malignancies. In previously treated metastatic castration resistant prostate cancer (mCRPC), a small subset of patients have a therapeutic response to checkpoint inhibition. Those who do respond to anti-PD-1/PD-L1 therapy have a marked, durable response to treatment, suggesting some derive long-term benefit from immune checkpoint blockade. In other cancers, one strategy to increase the efficacy of immune checkpoint blockade is to combine it with a pro-immune stimulatory agent, such as radiation. Here we present a case of a patient with heavily treated mCRPC who had a significant tumor response to concurrent pembrolizumab and radiation therapy to the primary prostatic mass. We review the growing evidence supporting the use of this combination therapy in other cancers and its potential benefit and safety in mCRPC. Our report highlights a potential therapeutic approach that should be further investigated in previously treated mCRPC.

Targeting CD38 and PD-1 with isatuximab plus cemiplimab in patients with advanced solid malignancies: results from a phase I/II open-label, multicenter study

“…12 An approach for increasing response to treatment is to identify combinations that synergize with immune checkpoint inhibitor therapy, potentially leading to enhanced therapeutic effects and durability. 13 The rationale for combining anti-CD38 and anti-PD-1 therapies is supported by studies in multiple myeloma, where data have shown that multiple myeloma cells increase expression of PD-1 by NK cells. 14 As a result, the PD-1/PD-L1 axis leads to suppressed antibody-dependent cellular toxicity mediated by isatuximab.…”

Adenocarcinoma of the Prostate: Future Directions for Translational Science

“…Patients with alterations in DNA repair genes may respond better to immunotherapies due to a higher tumor mutational burden and combining immune checkpoint blockade with PARP inhibitors may further improve the treatment outlook of this subset of castration resistance prostate cancer patients. Release of tumor antigens and immunostimulatory molecules following radiation-induced cell death may also boost the impact of immunotherapy regimens by increasing tumor immunogenicity (84)(85)(86). In addition, therapies that indirectly (for example, chemotherapies) or directly (for example, CSF1-R, CCL2 antagonists) target suppressive myeloid populations could further enhance T cell function and as a result immunotherapy efficacy.…”

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review (Part 6): Correlation of PD-L1 Expression with the Status of Mismatch Repair System, BRCA, PTEN, and Other Genes

“…In particular, increasing attention has been paid to immunohistochemical biomarkers such as Programmed death-1 (PD-1) and its ligand PD-L1, evaluating their ability to predict the response to immunotherapy drugs. PD-1 and PD-L1 are type-I transmembrane glycoproteins encoded by the PDCD1 gene (located on chromosome 2) and CD274 gene (located on chromosome 9), respectively: they are present on the surface of various immune cells, and PD-L1 may be expressed by tumor cells (including PC cells) [ 2 , 3 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , …”

“…However, PD-L1 constitutive expression could also be induced by genetic alterations (such as PTEN loss) or activation of signaling pathways (intrinsic immune resistance); epigenetic regulators may also interfere with PD-L1 expression [ 4 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 24 , 58 , 71 , 125 , 126 ]. Limited data are available for PC [ 8 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , ...…”