Could anti-PD-1 antibody be used as treatment for metastatic prostate cancer?
Researchers from Oregon Health & Science University (OHSU) Knight Cancer Institute (OR, USA) have demonstrated the clinical activity of the PD-1-targeting monoclonal antibody pembrolizumab in patients with metastatic prostate cancer.
These Phase II trial data contradict previous results, which presented no evidence of PD-1 immunotherapies having antitumor effects in patients with aggressive, advanced-stage prostate cancer.
In the study, published recently in Oncotarget, ten men with metastatic, castration-resistant prostate cancer were treated with pembrolizumab following no response to androgen receptor antagonist enzalutamide and androgen deprivation therapy.
Three of the first ten patients in the trial displayed swift reductions in prostate-specific antigen (PSA) levels; these participants started with serum PSA levels of 46, 71 and 2503 ng / ml, which fell sharply to under 0.1 ng / ml after treatment with the PD-1 blockade. The patients also remained free of progression at 30, 55 and 16 weeks, respectively.
Follow-up imaging scans further demonstrated positive results with the tumors shrinking in two of the three individuals, one of whom also displayed reduction in size of metastatic liver tumors. Moreover, two of the three patients that responded to treatment noted that they have gained relief from cancer pain and stopped taking opiate medications.
Lead study author Julie Graff (OHSU Knight Cancer Institute) commented: “It’s pretty remarkable, especially in light of the fact that many people doubted this approach could work at all. You don’t get responses like this with almost any other treatment.”
Important unknowns still remain; it is not possible to select which patients are likely to respond to this treatment and it is not yet known whether pembrolizumab improves survival in men with metastatic, castration-resistant prostate cancer.
Though three of the ten participants in the study presented with stable disease at 30, 47 and 50 weeks, four of the remaining patients did not display evidence of clinical benefit, with one of the four men dying of the cancer.
Graff and team, however, stated that the results of those that responded to treatment are clearly notable, with current approved agents for metastatic, castration-resistant prostate cancer seldom resulting in PSA reduction to less than 0.2 ng / ml post enzalutamide resistance. They added that responses in liver metastasis shown by this anti-PD-1 therapy are also rare with androgen receptor-targeting drugs and cytotoxic chemotherapies.
This Phase II study to evaluate the efficacy of pembrolizumab in this setting was inspired by the researchers’ previous reports on two participants who responded well to immunotherapy and hypothesized that immunotherapy could be enhanced by androgen receptor blockers.
As they wrote in their previous paper: “There are considerable data showing that androgen-ablation may augment an antitumor immune response. Enzalutamide therapy represents a more potent form of androgen suppression and may therefore be associated with previously underappreciated immune modulatory effects.”
Graff concludes by stating that the results are collated from the first ten patients, and therefore must be taken as preliminary. The ongoing study has enrolled additional patients and will provide more detailed answers about the potential benefits of PD-1-targeting therapy in men with metastatic prostate cancer.
Source: OHSU press release
