From the Research
Efficacy of PD-1 Targeted Therapy in Combination with Taxotere (Docetaxel) for Prostate Cancer
- The combination of PD-1 targeted therapy with docetaxel has shown promise in treating prostate cancer, with studies indicating improved prostate-specific antigen progression-free survival and overall response rates 1, 2.
- A study published in 2022 found that docetaxel-based chemohormonal therapy induced immunologic changes and potentiated checkpoint blockade immunotherapy in prostate cancer, resulting in better clinical outcomes when combined with anti-PD1 blockade 1.
- The KEYNOTE-921 study, a Phase III trial, aims to evaluate the efficacy and safety of pembrolizumab (a PD-1 inhibitor) plus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with a next-generation hormonal agent 3.
- Long-term results from the Phase 1b/2 KEYNOTE-365 Cohort B study showed that pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC, with a confirmed prostate-specific antigen response rate of 34% and a confirmed objective response rate of 23% 2.
- The role of PD-1/PD-L1 in prostate cancer prognosis and immunotherapy has been confirmed, with high PD-L1 expression associated with poor clinical outcomes and anti-PD-1/PD-L1 immunotherapy showing promise in combination with other treatments, including chemotherapy and vaccines 4.
Mechanism of Action
- Docetaxel has been shown to activate the cGAS/STING pathway in prostate cancer, inducing IFN signaling and resulting in lymphocyte infiltration, which may enhance the efficacy of PD-1 targeted therapy 1.
- The combination of docetaxel with PD-1 inhibitors may also upregulate the abundance of PD1 and PD-L1, sensitizing tumors to anti-PD1 blockade 1.
Clinical Implications
- The combination of PD-1 targeted therapy with docetaxel may offer a new treatment option for patients with mCRPC, particularly those who have progressed after treatment with next-generation hormonal agents 3, 2.
- Further studies are needed to fully evaluate the efficacy and safety of this combination therapy in prostate cancer patients 3, 2.