First-line Treatment Options for mCRPC

Alicia Morgans, MD, MPH: The first-line options for treatment of metastatic CRPC [castration-resistant prostate cancer] are numerous, and we make our decisions based on the treatments the patient has had prior, either for nonmetastatic CRPC or for metastatic hormone-sensitive prostate cancer.

For example, patients who have had treatment with intensified ADT [androgen deprivation therapy] for metastatic hormone-sensitive prostate cancer with abiraterone, enzalutamide, or apalutamide should receive a different approach for metastatic CRPC. Usually, it’s going to be a docetaxel chemotherapy and an ADT combination in that first-line setting. If a patient has had docetaxel in the metastatic hormone-sensitive setting, they would typically proceed with a shift in the mechanism of action to treatment with ADT plus abiraterone or enzalutamide.

For patients who have had treatment for nonmetastatic CRPC, we only have those AR [androgen receptor]–targeted agents as options for intensification with our ADT, and those patients typically get treatment with chemotherapy. It’s important to remember that there are other options; for patients who have relatively slowly progressing and asymptomatic disease, sipuleucel-T is an option. For patients who have DRD alterations, they could potentially get treatment with olaparib if they had previous treatment with an AR-targeted treatment combination with ADT. Finally, if patients have significant bone metastases and pain, they could even get treatment with radium.

There are a lot of options, and we make our treatment decisions for first-line metastatic CRPC based on the combinations of therapies the patient has had in the past.

Transcript edited for clarity.

A 70-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer

May 2017

Initial presentation

A 70-year-old man presents with nocturia and decreased appetite

Clinical workup

1. PMH: Unremarkable
2. PE: DRE, enlarged prostate
3. TRUS and biopsy revealed adenocarcinoma of the prostate gland, Gleason score 9 [5+4]
4. CT showed minimal nodal involvement
5. PSA 42 ng/mL, LDH 404 U/L
6. His ECOG PS is 1

Treatment

1. Patient started on ADT with initial PSA response 12 ng/mL

December 2017

1. Patient complained of right hip pain and abdomen pain
2. Imaging with CT and bone scan showed 2 metastatic bone lesions in the pelvis and diffuse liver lesions
3. PSA 30 ng/mL; Hb 9.4 g/dL; ANC 1.5
4. Patient started on docetaxel, 6 cycles completed
5. Follow-up imaging showed stable disease

November 2018

1. PSA 40 ng/mL
2. Routine imaging shows new metastatic bone lesions in the pelvis
3. Patient started on abiraterone and prednisone, after 6 months he has a restaging scan which shows continued progression of disease

January 2019

1. Patient had a 68Ga-PSMA-11 scan when screening for the VISION trial which shows several positive metastatic lesions in the pelvis and liver metastases
2. He qualified on screening and enrolled in a clinical trial and treated with 177Lu-PSMA-617 as per the VISION protocol (7.4 Gbq [100 mCi] every 6 weeks for 4-6 cycles)