Immunotherapy and Targeted Therapy for Prostate Cancer

Targeted therapies and immunotherapies are mainly used to treat advanced or recurrent prostate cancer. FDA approved drugs are listed below. Clinical trials using these agents may also be available for treatment of prostate cancer.

Immunotherapies 

Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells. 

• Immune checkpoint inhibitors are a type of immunotherapy most often used to treat advanced/metastatic prostate cancer that have MSI-H or dMMR; usually after other treatments have been tried.
  • Keytruda (pembrolizumab) may be used to treat patients with castration resistant prostate cancer that is MSI-H or dMMR and have had one line of therapy affecting the whole body.
• Cancer treatment vaccines are a type of immunotherapy that uses a patient’s own cancer cells to boost their immune system.
  • Provenge (sipuleucel-T) may be used to treat patients with metastatic prostate cancer whose disease has progressed aftger hormonal treatment who have either no or very minimal symptoms related to the prostate cancer.

Targeted therapies

Targeted therapies are drugs that are designed to attack specific changes found in cancer cells. Several different targeted therapies are used to treat prostate cancer. 

PARP inhibitors

PARP inhibitors are targeted therapies that were developed for, and work best in people with a BRCA1 or BRCA2 mutation. The following PARP inhibitors are used to treat mCRPC. 

• The PARP inhibitor Talzenna (talazoparib) may be used as a first-line treatment for mCRPC in people who have an inherited mutation found through genetic testing or tumor mutation found through tumor testing in BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C.
• The PARP inhibitor, Lynparza (olaparib) may be used in combination with Zytiga and prednisone or prednisolone for the first-line or later treatment of mCRPC in patients with an inherited BRCA1 or BRCA2 mutation (found through genetic testing) or tumor BRCA1 or BRCA2 mutation (found through tumor testing or liquid biopsy). 
• The PARP inhibitor, Lynparza may be used to treat mCRPC after the cancer has progressed on the drugs Xtandi (enzalutamide) or Zytiga (abiraterone) in people with an inherited mutation in BRCA1, BRCA2 (found through genetic testing) or a tumor mutation in BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L (found through tumor testing).
• The PARP inhibitor, Rubraca (rucaparib) may be used to treat mCRPC, in people who have an inherited mutation in BRCA1 or BRCA2 (found through genetic testing) or a tumor mutation in BRCA1 or BRCA2 (found through tumor testing or liquid biopsy).
• Akeega is a new drug that combines the PARP inhibitor, Zejula (niraparib) with the hormone therapy, Zytiga. Akeega is used with prednisone to treat mCRPC in people who have an inherited mutation or a tumor mutation in BRCA1 or BRCA2 (found through tumor testing or liquid biopsy).

Other targeted therapies

• Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is used to treat mCRPC for men previously treated with with hormone therapy with an androgen receptor inhibitor and taxane-based chemotherapy. 

Table of targeted and immunotherapies for prostate cancer

Name of drug	Cancer stage	Indication	Biomarker or genetic test	Type of agent
Akeega (niraparib and abiraterone acetate)	Metastatic castration-resistant prostate cancer (mCRPC)	In combination with prednisone for first-line or later treatment of mCRPC	Inherited or tumor mutation in BRCA1 or BRCA2 based on FoundationOne tumor test	PARP inhibitor combined with a hormonal therapy
Lynparza (olaparib)	Metastatic castration-resistant prostate cancer (mCRPC)	Combined with Zytiga and prednisone or prednisolone for first-line or later treatment of mCRPC	Inherited mutation in BRCA1 or BRCA2 found through genetic testing or tumor BRCA1 or BRCA2 mutation found through tumor testing or liquid biopsy.	PARP inhibitor
		For treatment of mCRPC which has progressed following treatment with Xtandi (enzalutamide) or Zytiga (abiraterone)	Inherited mutation in BRCA1 or BRCA2 or tumor mutation one of the following genes: ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK2, FANCL, PALB2, RAD51B, RAD51C,  RAD51D ,  RAD54	PARP inhibitor
Rubraca (rucaparib)	Metastatic castration-resistant prostate cancer (mCRPC)	For treatment of mCRPC which has been treated with androgen receptor-directed therapy and a taxane-based chemotherapy	Inherited or acquired (tumor) mutation in BRCA1 or BRCA2	PARP inhibitor
Talzenna  (talazoparib)	Metastatic castration-resistant prostate cancer (mCRPC)	In combination with enzalutamide for mCRPC which has not yet been treated in the castration-resistant setting	Inherited or tumor mutation in one of the following genes: BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C	PARP inhibitor
Pluvicto (lutetium Lu 177 vipivotide tetraxetan)	Metastatic castration-resistant prostate cancer (mCRPC)	For treatment of mCRPC which has stopped responding or got worse after treatment with hormonal therapy using an androgen receptor inhibitor and taxane-based chemotherapy	Imaging with a PET scan that looks for prostate cancers with the marker PSMA	Targeted radiation therapy
Provenge (sipuleucel-T)	Metastatic castration resistant prostate cancer (mCRPC)	For the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer	No biomarker needed	Cancer vaccine
Keytruda (pembrolizumab)	Metastatic or unresectable solid tumors	For treatment of solid tumors that have progressed after treatment and for which there are no other treatment options	MSI-H (Microsatellite Instability High) or MMR-D (Mismatch Repair Deficiency)	Immune checkpoint inhibitor
Keytruda (pembrolizumab)	Metastatic or unresectable solid tumors	For the treatment of solid tumors that have progressed following prior treatment and for which there are no satisfactory alternative treatment options	Tumor Mutational Burden High (TMB-H)	Immune checkpoint inhibitor
Vitrakvi (larotrectinib)	Metastatic solid tumors	For treatment in metastatic solid tumors where surgical resection is likely to result in severe morbidity, and  for which there are no satisfactory alternative treatments or the cancer progressed following treatment	NTRK fusion	Kinase inhibitor