Role of PARP Inhibitor Plus Abiraterone for Patients With mCRPC

EP: 1.Patient Profile: A 65-Year-Old Man With Prostate Cancer

EP: 2.Testing for BRCA Mutations and HRR Status in Prostate Cancer

EP: 3.First-Line Therapy Options for mCRPC

EP: 4.PROpel: Olaparib and Abiraterone for Patients with mCRPC

EP: 5.Recent PARP Inhibitor Data in Prostate Cancer

EP: 6.Treatment Considerations for PARP Inhibitors in mCRPC

Now Viewing

EP: 7.Role of PARP Inhibitor Plus Abiraterone for Patients With mCRPC

EP: 8.Non-BRCA HRD Mutations and Rechallenging with PARP Inhibitors in mCRPC

EP: 9.Managing Adverse Events Associated With PARP Inhibitors in Prostate Cancer

EP: 10.Clinical Pearls for Community Oncologists Treating Prostate Cancer

Case: A 65-Year-Old Man With Prostate Cancer

January 2018

Initial Presentation

• A 65-year-old man was diagnosed with localized prostate cancer
• Biopsy revealed adenocarcinoma of the prostate gland, Gleason score 7 [4+3]
• PSA 15.7 ng/mL
• Baseline staging: T3bN1M0 with right seminal vesicle and pelvic lymph node involvement

Initial Treatment

• He undergoes radical prostatectomy with PLND
  • PSA nadir of 0.4 ng/mL post-surgery
  • Gleason 7 (4 + 3) confirmed
  • Positive surgical margins
  • Baseline staging confirmed – AJCC Stage IVA

February 2019

Follow-Up Notes

• Serum PSA, 38 ng/mL; ALP, 289 IU/L
• PSMA PET CT:
  • Metastatic retroperitoneal LNs outside resection field
  • Abdominal nodes
  • Bone mets in ribs and thoracic spine
• Genetic testing: BRCA2 mutation-positive

Additional Treatment

• Abiraterone + prednisone initiated
• Improved pain, PSA, and ALP

October 2019

Follow-Up Notes

• Patient reported bone pain
• Laboratory testing revealed rising PSA and ALP (serum PSA, 350 ng/mL; ALP, 2500 IU/L)
• Imaging showed radiologic progression
• ECOG PS 1
• PSMA PET CT: increased uptake in retroperitoneal and abdominal LNs

mCRPC Treatment

• Treated with docetaxel x4 cycles and denosumab
  • Serum PSA, 38 ng/mL; ALP, 289 IU/L
  • Reporting bone pain increased in back, now reporting pain in hip area
• Bone scan and CT scan:
  • Enlargement of retroperitoneal and abdominal LNs
  • Additional bone mets noted in pelvic region

Transcript:

Daniel J. George, MD: When I think about the practice today for patients with metastatic castrate-resistant prostate cancer, despite the overwhelming level 1 evidence for using novel hormonal agents early, there are still going to be circumstances where we have patients for whom we don’t use a novel hormonal agent early in the disease course. A couple of these would be patients who are presenting with locally advanced disease and we’re starting on androgen deprivation therapy and radiation therapy, our standard of care, 2 years of androgen deprivation therapy. Some patients within that 2-year period are going to progress, and those patients who develop early progression with hormones and radiation, they’re castrate-resistant. If those patients have metastatic disease, and with much of our novel imaging, we’re going to find these are the reasons these patients are progressing, not within their radiated prostate bed, but outside of that radiation bed. That progression will be seen either on traditional or novel imaging. These are the patients today who I think are best representative of the PROpel data. If they’re BRCA-mutated, these are the patients for whom I’m going to want to consider using androgen deprivation therapy, a novel hormonal agent like abiraterone, and a PARP inhibitor like olaparib. It’s precisely because of the PROpel data and how powerful they are that I want to use that in somebody like that, who has this accelerated course progression to castration resistance within the first 2 years of hormones and radiation.

Another scenario is like the case we presented here, where somebody had a BRCA mutation up front, rapid progression following surgery, relatively rapid progression following androgen deprivation therapy and abiraterone, and then further progression after response to docetaxel chemotherapy. Because the patient had a prior response to abiraterone, due to a break from abiraterone with docetaxel, I’d consider rechallenging that patient with abiraterone and adding olaparib. Because now they’re somebody who falls into the PROfound study situation, where our expectations for median progression-free survival are modest, maybe 7 months or so. That’s the population of patients where I’d like to extend it as much as possible. This olaparib use is going to be the best last treatment we can offer that patient with a BRCA mutation, so we’re going to want to maximize it however we can. If they tolerated the abiraterone well, I’m going to want to rechallenge that with my olaparib to see if I can get anywhere close to the results we saw with PROpel rather than the results we saw with PROfound.

Those are some of the scenarios where I think even today, despite the use of our novel hormonal agents increasing in the hormone-sensitive disease space, there’s still room for these PROpel data to use them and extrapolate them into our practice.

Transcript edited for clarity.