Targeted Drug Therapy for Prostate Cancer

As researchers have learned more about some of the changes inside prostate cancer cells that help them grow, they have developed newer types of drugs that target these changes. These targeted drugs work differently from chemotherapy (chemo) and hormone therapy drugs. They sometimes work when these other types of drugs don’t, and they often have different side effects.

Like chemo and hormone therapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against some cancers that have spread to distant parts of the body.

PARP inhibitors

Rucaparib (Rubraca) and olaparib (Lynparza) are drugs known as a PARP (poly(ADP)-ribose polymerase) inhibitors. PARP enzymes normally help repair damaged DNA inside cells.

The proteins coded for by the BRCA genes (BRCA1 and BRCA2) also normally help repair DNA, but in a different way, and mutations (changes) in one of these genes can stop the BRCA proteins from working like they should.

By blocking the PARP proteins as well, these drugs make it very hard for tumor cells with an abnormal BRCA gene to repair damaged DNA, which often leads to the death of these cells.

Your doctor will likely test your blood or saliva and your cancer cells to be sure the cells have a BRCA gene change before starting treatment with a PARP inhibitor.

These drugs are taken by mouth as pills, typically twice a day. They are given along with hormone therapy such as an LHRH agonist or after an orchiectomy.

Rucaparib (Rubraca) can be used to treat metastatic, castration-resistant prostate cancer that has grown after treatment with taxane chemotherapy (such as docetaxel or cabazitaxel) and hormone therapy, and when the cancer cells have a change in one of the BRCA genes.

Olaparib (Lynparza) can be used to treat metastatic, castration-resistant prostate cancer, either:

• Along with the hormone therapy drug abiraterone (and a steroid drug such as prednisone), if the cancer cells have changes in one of the BRCA genes
• By itself, if the cancer has grown after getting a hormone therapy drug such as enzalutamide or abiraterone, and the cancer cells have a change in one of the BRCA genes (or other DNA repair genes)

Talazoparib (Talzenna) can be used to treat metastatic, castration-resistant prostate cancer that have homologous recombination repair (HRR) gene mutation(s) and have not received any prior treatment for castration-resistant disease. Talazoparib has been approved to be given with enzalutamide once per day. HRR genes include: ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, and RAD51C.

Side effects of PARP inhibitors

Side effects of these drugs can include nausea, vomiting, diarrhea, fatigue, loss of appetite, low red blood cell counts (anemia), constipation, skin rash, abnormal liver blood tests, low blood platelet counts, cough and shortness of breath.

Rarely, some people treated with these drugs might develop a blood cancer later on, such as myelodysplastic syndrome or acute myeloid leukemia. Some men taking olaparib might develop blood clots in the lungs or legs.