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3yr
PARP inhibitors for the treatment of prostate cancer

Olaparib (Lynparza) and rucaparib (Rubraca) are both PARP inhibitors approved for mCRPC patients following AR therapy. Olaparib was the first PARP inhibitor approved, allowing it to gain a lead in the market, after the patients in the treatment arm of the Phase III PROpel trial achieved a median OS of 19.1 months and an rPFS of 5.8 months in the overall homologous recombination repair deficient cohort. Rucaparib received approval following positive results from the Phase II TRITON2 trial, where patients with measurable disease and BRCA mutations achieved a median ORR of 43.5% after rucaparib treatment.

Two other PARP inhibitors are currently in development for prostate cancer: talazoparib (Talzenna) and niraparib (Zejula). Neither therapeutics have late-phase data available in this indication, but talazoparib -treated patients with BRCA mutations in the Phase II TALAPRO-1 trial showed an rPFS of 9.3 months, whilst niraparib-treated patients had an rPFS of 8.2 months and an OS of 12.6 months in the Phase II GALAHAD trial.

Share your thoughts on the efficacy shown by both talazoparib and niraparib, and based on this data, if either drug is approved, how would this likely change your prescribing practices?

  • 3yr
    Sounds like promising Data to push Parp inhibitors more into to treatment paradigm. Currently Lynparza is at the forefront for prostate cancer treatment in this patient population
  • 3yr
    the data is quite impressive and would be eager to use although still need to deal with cost and toxicity issues as these drugs can be difficult to tolerate in older patients with GI issues
  • 3yr
    The use of PARP inhibitors in prostate cancer expands the treatment options. It is also very difficult to interpret / compare the different trials, but the OS associated with Propel trialI think puts Olaparib as the preferred PARP inhibitor.
  • 3yr
    It is very encouraging that new immunotherapy is available and becoming available for the post androgen blockade patients. The pendulum swing back to medical oncologists seems to be occuring
  • 3yr
    Although they are not compared head-to-head I would contrast the efficacy/tolerability. Olaparib seems to have the most favorable profile.
  • 3yr
    It is always nice to have choices since the patient may have problems tolerating one PARP but do fine with a different agent. Talazoparib is a once a day drug and that may help with compliance. Efficacy between the different PARPis seems similar so it will be hard to choose between them based on that criterion alone.
  • 3yr
    These look okay but the oliparib studies are more robust in this group of patients. Unless the phase iii studies of either of these drugs is something amazing I don’t think we will use them much.
  • 3yr
    Will have to wait and see tolerability and long term efficacy data. I currently use Lynparza for HRD prostate cancer as well.
  • 3yr
    both drugs are clearly effective but without head to head data it is hard to tell for any PAPR is better. I think they are all very similar and I would use oalparib based on habit and experience
  • 3yr
    Usually Use olaparib when a PARP inhibitor is indicated. All the PARP inhibitors likely similar but will look at the data as they come in and decide.
  • 3yr
    This is truly an exciting area development for metastatic prostate cancer. I am old enough to remember when there was virtually no treatments at all for this dreaded disease. So I am very heartened to see all of the bass mount of research that is being done to combat and delay progression of this cancer.
  • 3yr
    I find it interesting that the rPFS of Zejula was better than that of Lynparza and Rubraca but the OS was less than. Again, hard to compare apples to apples without head to head trial. The real question is why use Zejula and Talzenna over the current approved PARPi that are currently available?
  • 3yr
    Olaparib is my go to Parp inhibitor since it has the most data. Fairly well tolerated. I’ll wait for more data before incorporating the latter parp inhibitors in my practice.
  • 3yr
    I use Lynparza for the HRD prostate cancer and have seen approximately 9 months of PFS. this is a germline mutation
  • 3yr
    Agree long term f/u is needed
  • 3yr
    I have used Olaparib in my metastatic prostate cancer pt and so far the tolerance has been great. would wait to see the PFs and Os data on Talazoparib and Zejula.
  • 4yr
    Thanks, All, for your wonderful input! What is your clinical experience with PARP inhibitors? In general, how do patients fare on this treatment?
  • 4yr
    They all probably about the same. I have used all PARPs except for Talzenna. I think full dose Zejula is too harsh but it is not approved for prostate. I can't make out difference between Rubraca and Lynparza. Lynparza though has easier label and approval process
  • 4yr
    Paribs are used to treat prostate cancer but those last 2 meds are still being studied
    talazoparib is now being used for Rx of breast Ca So the Jury is still out
  • 4yr
    What are the perceived benefits/drawbacks of talazoparib and niraparib?
  • 4yr
    Both have meaningful clinical benefits but long term follow up is still needed
  • 4yr
    The median OS of 19.1 months shown by Olaparib puts it, to my mind, as the leader among PARP inhibitors in treatment of mCRPC. I will await longer-term results for both talazoparib and niraparib before adopting them.

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