Two Phase III trials of PARP inhibitors in mCRPC


There are now two, ongoing, Phase III trials of PARP inhibitors in the treatment of eligible patients with metastatic, castration-resistant prostate cancer (mCRPC).

The PROfound trial

The PROfound trial is now enrolling eligible patients with mCRPC at more than 150 centers around the world. It is a randomized, multi-center trial designed to explore whether treatment with the PARP inhibitor olaparib (Lynparza) can extend survival of eligible patients who have already progressed on treatment with a prior new hormonal agent.

To be eligible, patients must

  • Have documented evidence of mCRPC
  • Have progressed on a prior new hormonal agent (e.g., abiraterone acetate and/or enzalutamide) for the treatment of mCRPC
  • Be having ongoing therapy with an LHRH analog or have had a bilateral orchiectomy
  • Have radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy).
  • Have one of 15 genes involved in the homologous recombination repair (HRR) pathway in their cancer tissue

Patients will also be stratified into two cohorts:

  • Cohort A will include only patients (n = 240) with mutations in BRCA1, BRCA2 or ATM.
  • Cohort B will include patients (n = 100) with a mutation in any one of 12 other HRR genes.

The trial is thus designed to enroll about 340 patients. About 226 of these patients patients will be randomized to treatment with olaparib, and the other 114 will be randomized to treatment with either enzalutamide or abiraterone acetate (as selected by the individual investigator for each individual patient); i.e., patients are being randomized 2:1 to olaparib or to one of the two new hormonal agents.

For more information about this trial see the information either on ClinicalTrials.gov or in the abstract of the poster being presented at ASCO.

The TRITON3 trial

The TRITON3 trial is in many ways similar to the PROfound trial but there are differences and it uses a different PARP inhibitor — the drug rucaparib (Rubraca).

In this trial, eligible patients must

 

  • Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate
  • Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
  • Be eligible for treatment with physician’s choice of a comparator treatment (abiraterone acetate, enzalutamide, or docetaxel)
  • Experienced disease progression after having received one prior next generation androgen receptor-targeted therapy for castration-resistant disease
  • Have a deleterious mutation in a BRCA1/2 or ATM gene

In other words, patients with only three as opposed to any one of 15 different HRR mutations are eligible for enrollment in this trial.

The TRITON3 trial is currently enrolling up to about 400 patients at 12 different centers in the US only, and eligible patients will be randomized 2:1 to either

  • Treatment with rucaparib or
  • Treatment with abiraterone acetate, enzalutamide or docetaxel chemotherapy (as recommended by the treating physician)

Thus about 266 patients will be treated with rucaparib and 134 patients will be treated with one of the comparator drugs.

For more information about this trial, you can again see the information either on ClinicalTrials.gov or in the abstract of the poster being presented at ASCO.

 

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