Bottom line:  Dr. Maha Hussain states that olaparib (Lynparza) for patients with selected DNA damage repair gene alterations (BRCA1/2, ATM) should represent a new standard of care for mCRPC patients who have progressed on abiraterone or enzalutamide, regardless of prior treatment with taxane chemotherapy.   This bodes well for eventual FDA approval of olaparib for metastatic, castrate-resistant prostate cancer patients who harbor DNA Damage Repair (DDR) mutations.

Details:

The PROfound study is a Phase III, randomized, multicenter trial evaluating the efficacy and safety of the PARP inhibitor olaparib versus physician’s choice of enzalutamide or abiraterone acetate in pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients with a qualifying homologous recombination repair (HRR) gene mutation.

In order to be included in the study, patients had to have mCRPC, have had disease progression on either enzalutamide or abiraterone, and have alterations in one more pre-selected DNA damage repair genes as assayed by the customized FoundationOne® sequencing test (https://www.foundationmedicine.com/ ). Patients with a DNA damage repair (DDR) alteration were stratified into 2 cohorts: (1) Cohort A with BRCA1, BRCA2 or ATM alterations, as these have the strongest preclinical and prior trial support data, and (2) Cohort B with 12 other DDR alterations.  Both cohorts proved superior to treatment with enzalutamide or abiraterone + prednisone, but Cohort A (BRCA1/2, ATM) demonstrated the best response.

Treatment in these cohorts were reasonably well tolerated in this group of patients, though more adverse events were reported in the olaparib arm than in the Abi/Enza arm. Anemia, nausea, fatigue, asthenia and decreased appetite were the most common adverse effects, with anemia seen in 21% of patients.

For the full summary of the trial presented at ESMO 2019 Conference, click here: http://tiny.cc/Olaparib