Second-line and Beyond: Treatment of mCRPC


Dr. Morgans talks about available second-line treatment options for patients with mCRPC and considerations when choosing second and subsequent-line treatment options.

Alicia Morgans, MD, MPH: Treatment for metastatic CRPC [castration-resistant prostate cancer] in the second- and third-line settings and beyond is very similar to the way that we treat metastatic CRPC in the first line. What I mean by that is, we must think about what the patient has had in the past as we’re trying to make decisions for that patient’s current and future treatment. As a team, we need to consider the patient’s preferences, the patient’s clinical status, and of course whether the patient has had exposure to AR [androgen receptor]–targeted agents, chemotherapy, radium, or other things that make it less likely they’ll respond to future agents like an AR-targeted agent followed by an AR-targeted agent—that’s unlikely to be effective—or that may have changes in their bone marrow or their tolerability to get other treatments.

If the patient has had chemotherapy and has an anemia due to marrow suppression related to chemotherapy exposure, radium may be a more challenging treatment to give. Ultimately, it’s a combination of our patient’s clinical factors, the disease characteristics in terms of where the metastatic disease is, the patient’s preferences, and prior treatments that come together to help us choose treatment options for our patient going forward.

Alternative second-line mCRPC for this patient might include cabazitaxel, which is a chemotherapy that can be used after disease has progressed on docetaxel and an AR-targeted agent. It’s a good option, as we’ve seen in the CARD trial for controlling prostate cancer, particularly if there are liver metastases as in this case. 177Lu-PSMA-617 may be an option for us to use in the future because that’s what this patient got in a clinical trial. There’s a phase 2 trial that attempts to compare tolerability, PSA [prostate-specific antigen] response, and radiographic progression-free survival between cabazitaxel and lutetium. That trial is the TheraP trial, which was performed by a team of oncologists, nuclear medicine doctors, and urologists in New Zealand and Australia and was presented about a year ago. In that trial we noticed that cabazitaxel, which is known to be quite effective in this third-line setting, did not have as strong of a PSA-suppressive response or as long of a radiographic progression-free survival as lutetium. However, it should be noted that this is a phase 2 trial and isn’t substantial enough to change treatment, particularly because lutetium is not approved for the treatment of metastatic CRPC. This certainly adds to our clinical decision-making and may be important for patients and clinicians, should Lutetium177 be approved, because they’re deciding between those 2 agents in the third-line setting.

When choosing any line of therapy, particularly as we get to third line and beyond, it’s very important that we ensure we understand all options of treatment available to our patient. We must remember radiopharmaceuticals that have already been approved, like radium. We must remember to do germline and somatic sequencing to see if our patient is eligible for treatment with a PARP inhibitor. Somatic sequencing gives us the opportunity to identify MSI [microsatellite instability]–high status, which allows the patient the opportunity to be treated with pembrolizumab. Understanding all the options, including whether a patient has the opportunity to enroll in a clinical trial, can help us ensure that our patient is given every opportunity to have the disease controlled, to feel better, and to optimize their time.

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


  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)
Related Videos
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Daniel J. George, MD, an expert on prostate cancer
Related Content