PARP inhibitor has positive outcomes in Phase III trial in selected men with mCRPC

According to a media release issued jointly yesterday by AstraZeneca and Merck, treatment with the PARP inhibitor olaparib (Lynparza) has demonstrated “positive results from the Phase III PROfound trial … in [a subset of] men with metastatic castration-resistant prostate cancer (mCRPC).”

Specifically, according to the corporate media release, the results of the 340-patient PROfound trial are said to have demonstrated “statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS)” of olaparib in treatment of men with mCRPC who have an homologous recombination repair gene mutation (HRRm) and who have progressed on prior treatment with new hormonal anticancer treatments (e.g., enzalutamide and abiraterone). The subpopulation of “homologous repair gene mutations” referred to are the BRCA1/2 and ATM gene mutations, so this is a small subset of men with mCRPC.

There appear to be no data yet to suggest that such treatment has any impact on the patients’ overall survival.

Also according to the media release, “the safety and tolerability profile of [olaparib] was generally consistent with [data from] previous trials.”

The companies further state that they “plan to present the full data from the trial at a forthcoming medical meeting.” It is possible that such a presentation might occur at a meeting early in 2020, but it could also be later this year. We should also assume that the companies will be seeking regulatory approval in the US and elsewhere for the use of olaparib in the treatment of men with mCRPC who have progressed on treatment with drugs like enzalutamide and abiraterone acetate who also carry relevant BRCA1/2 and ATM gene mutations.

2 Responses

  1. Mike:

    Just to be clear for our readers, these BRCA1, BRCA2, and ATM mutations were “somatic” (from tumor tissue), correct? That means these weren’t hereditary, “germline” mutations found from saliva testing. Just checking … didn’t see it in Astra Zeneca’s press release, but I says it in the clinical trial listing.


  2. Jan:

    What it says in the clinical trial inclusion criteria is that patients had to have a “Qualifying HRR mutation in tumor tissue.”

    What this means is that the qualifying mutations had to be identifiable in tumor tissue. However, what this does not mean is that the mutations were all necessarily exclusively somatic. A man with a hereditary BRCA2 mutation (for example) would normally still express such a mutation in a cancerous cell in his body if he was to get prostate cancer, so such a mutation would be expressed both through standard germline testing and through testing of the somatic tumor tissue.

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