Treatment Options in Metastatic Prostate Cancer

Alicia Morgans, MD, MPH:When deciding treatment for patients with metastatic CRPC [castrate-resistant prostate cancer] after progression on an androgen receptor [AR]—directed therapy, I certainly consider whether the disease is symptomatic or asymptomatic. We could consider using sipuleucel-T in patients who have a low burden of metastatic disease and are completely asymptomatic. We are also thinking about whether they have liver metastases, because we did not test sipuleucel-T in the phase III trial that led to its approval in patients with liver metastases.

With this patient, we know that he has had some symptoms and actually a high PSA [prostate-specific antigen] at the time of his recurrence. Usually we think about things like sipuleucel-T in patients who do not have any pain or are relatively asymptomatic, and who also have a relatively low PSA. Those are the patients in whom we think it will work best.

In this patient, I would also think about other exposures. This patient also had chemotherapy. And so in the setting of exposure to an androgen receptor—directed therapy and chemotherapy, I would want to change the mechanism of action away from an androgen receptor–directed therapy and focus on things like PARP inhibitors if the patient had DNA-repair defect; another chemotherapy if the patient did not have that defect; or potentially radium, which could be an option in patients who only have bone metastases, no lymph node metastases, and no visceral disease.

For this patient, we know he actually started with lymph node metastatic disease, so radium would not be expected to maintain disease control because it does not affect any disease outside the bone. For this patient, chemotherapy is the choice I would make. Even though he’s had progression on docetaxel chemotherapy, we know that switching to cabazitaxel chemotherapy can be highly effective both in terms of pain control and also in prolonging life.

When I think about tolerance to chemotherapy, particularly the tolerance of cabazitaxel, I think about some studies that were done post marketing, essentially, for cabazitaxel that demonstrated that cabazitaxel at the 20 mg/m²dose actually had less fatigue and less neuropathy than docetaxel at a standard dose of 75 mg/m². Cabazitaxel in my clinic, and certainly in those trials, is actually quite well tolerated, even in older patients.

What we saw in the CARD trial was that cabazitaxel was actually better tolerated than a second-line AR-targeted agent in patients who had already had progression on AR-targeted agent and at least 1 line of chemotherapy. In those patients, patients had a longer time to pain progression and had a better pain response than patients treated with a second AR-targeted agent. These patients felt better than those patients on what we normally consider to be quite tolerable treatments. And so even in older patients or in patients who have pain, cabazitaxel chemotherapy can be well tolerated with relatively low neuropathy and fatigue compared with other chemotherapy agents, and certainly we’d want to support these patients with our supportive measures. We can get them through it, and they seem to tolerate it quite well.

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