Published data on activity of olaparib in some men with mCRPC

A paper in the New England Journal of Medicine now provides detailed information about the activity of the PARP inhibitor olaparib in the treatment of carefully selected patients with metastatic, castration-resistant prostate cancer (mCRPC). We had mentioned these data previously when they were first presented at a meeting of the American Association for Cancer Research back in April this year.

The new paper by Mateo et al. (which is available as a full text article) addresses the results of the Phase II clinical trial of olaparib (Lynparza/AstraZeneca) in the treatment of 50 men with mCRPC — all of whom had been treated previously with docetaxel, most of whom (49/50, 98 percent) had been treated with abiraterone or enzalutamide, and some of whom (29/50, 58 percent) had also been treated with cabazitaxel.

The authors demonstrate that:

  • 16/49 evaluable patients (33 percent) exhibited a response to treatment with olaparib.
  • 12/16 patients exhibiting a response remained on olaparib therapy for 6 months or longer.
  • 16/49 patients could be identified as having homozygous deletions, deleterious mutations, or both in DNA-repair genes (e.g., the BRCA1/2 genes and others).
  • 14 of these 16 patients (88 percent) exhibited a response to olaparib, including
    • All 7 patients with BRCA2 loss
    • 4/5 patients ATM aberrations.
  • The specificity of the biomarker suite was 94 percent.
  • The most common grade 3 or grade 4 side effects to treatment with olaparib were
    • Anemia (in 10/50 patients, 20 percent)
    • Fatigue (in 6/50 patients,  12 percent)

The authors conclude that:

Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate.

The critical question that is going to be important in understanding how to use this new knowledge is whether — if olaparib is used earlier in the course of their disease to treat men with progressive prostate cancer and defects to DNA repair mechanisms — it may be possible to place these men into significantly longer-term remissions.

Treatment of such men after they have progressed on docetaxel and either abiraterone or enzalutamide (not to mention cabazitaxel) is unlikely to extend life significantly, but if olaparib works when given earlier (either alone or in combination with other agents)  we may be looking at a very different type of clinical opportunity.

3 Responses

  1. Hoping Lynparza works for me and other men on it. I had a CDK12 alteration which can cause genomic instability.

    I just started a week ago and so far it’s been very tolerable. Especially hope it doesn’t further whack my low blood counts. Blood work next week so I’ll see.

    All the best!

    PS: Recommend to men with advanced disease to have a new biopsy (bone or soft tissue) and have it analyzed by Foundation 1, etc., for actionable alterations. You may get lucky.

  2. Might be worth mentioning in your summary, Mike, that it was UK-based research?


    Richard L.

  3. Dominic:

    How has it gone with Lynparza? I am going to start that treatment in a week or 10 days. I had a Foundation One analysis last summer and have the BRCA2 marker among others.


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