Therapy Approach in High-Risk Prostate Cancer

Alicia Morgans, MD, MPH:When I think about treating patients with metastatic CRPC [castrate-resistant prostate cancer], I really think about all the agents we have at our disposal, and there are many. The most important thing to me, when I’m thinking through their next treatment, is understanding what they had in the past and how we can use a different mechanism of action for their next line of treatment to really sequence 1 therapy after another, hopefully prolonging time and quality of life multiple times over by sequencing very available treatment options that patients have over time. For example, if a patient has had an AR [androgen receptor]—targeted agent and docetaxel chemotherapy, the things I think about next are going to be something with a new mechanism of action or something that has demonstrated that after those 2 agents, it can be still effective in terms of prolonging life and making people feel better.

The option could be, in an asymptomatic patient, sipuleucel-T. Although if this is a more heavily pretreated population, most patients really seem to benefit with sipuleucel-T. For cabazitaxel chemotherapy, we now have the CARD data to show that we can certainly sequence it and, in the third-line setting, prolong life and improve quality of life. Or perhaps we could use radium in patients who only have bone metastases and no lymph node metastases or visceral metastases.

I also always think about sequencing a patient’s DNA as well as the tumor DNA to understand whether there are genetic germline mutations that may be targetable or somatic genomic mutations in the tumor tissue. We can use PARP inhibitors to potentially target these DNA-repair defect mutations that make patients sensitive to these drugs.

I also think about clinical trials and really expanding the options for patients by giving them something that’s not yet FDA approved. There are multiple things, whether they’re radiopharmaceuticals, androgen receptor—degrading agents, or other combinations that may be effective that we’re really just starting to understand. And these options are really only available through clinical trials, so that is always something I think about as well.

The landscape of treatment for metastatic CRPC is changing rapidly and dramatically with options demonstrating efficacy in both prolonging overall survival as well as maintaining quality of life. This includes treatments we’ve already had approved, like cabazitaxel, as well as things that are on the horizon, like PARP inhibitors. And it also includes things that are still to come, things like radiopharmaceuticals or other agents, whether they are vaccines, androgen receptor—degraders, or other approaches that are newly here for our patients.

There are so many options that it’s important for us to consider what patients have had before and think about changing the mechanism of action, or using treatments that we know can be effective after exposure to these other agents, to get the best results for our patients and not waste time with things that we think have a very low likelihood of working. Because when we waste time, it’s not only the potential for other treatments that we waste, but patients’ quality of life suffers as well. The landscape is changing, there are many opportunities, and it’s an exciting time to be a treating physician for men with metastatic CRPC.

Transcript edited for clarity.

Case: A 75-Year-Old Male with Metastatic Castrate-Resistant Prostate Cancer

Initial presentation

2015

• A 75-year-old man presented with intermittent right hip pain and decreased appetite
• PE: abnormal digital rectal exam, otherwise unremarkable

Clinical workup

• PSA 38 ng/mL, LDH 415 U/L
• Staging bone scan and abdominal/pelvic CT scan demonstrated localized disease
• Core needle biopsy with TRUS showed adenocarcinoma of the prostate
• Diagnosis: Stage T2N0M0 — intermediate risk adenocarcinoma of the prostate
• Gleason grade group 5
• ECOG PS 1

Treatment and Follow-Up

• EBRT + ADT was initiated; stable disease, completed 18 months of ADT
  • 6-months follow-up at undetectable PSA

2017

• He complained of increasing hip pain, new onset back pain and urinary frequency
• PSA 29.4 ng/mL              
• Bone scan showed evidence of two osteoblastic lesions in the right hip (0.8 cm and 1.1 cm)
• Abdominal/pelvic CT showed a 2.1 cm left pelvic mass; evidence of inguinal, iliac and axillary lymph node involvement
• He was re-staged to T2N1M1b - IVB
• Started treatment on enzalutamide 160 mg PO qDay

2018

• After 8 months on enzalutamide PSA 60.7 ng/mL
  • Abdominal/pelvic CT showed enlargement of left pelvic mass and progressive adenopathy
  • Bone scan revealed progression of disease
  • Patient was started on docetaxel 75 mg/m2 IV q3W + daily prednisone 5 mg POq12hr
  • After 4 cycles patients suffered from mild bilateral digital neuropathy, pitting of the nails, fatigue and stomatitis; due to toxicities docetaxel was discontinued
    • PSA 75.1 ng/mL, LDH 870 U/L
  • Cabazitaxel 20 mg/m²IV q3W + prednisone 10 mg PO qDay + pegfilgrastim was initiated