Olaparib Trial Offers a Look at Precision Medicine's Future

Maurie Markman, MD


March 20, 2015

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Hello. I am Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia, Pennsylvania. I want to briefly discuss an extremely interesting paper; in fact, I might go as far as to say that it is a landmark paper in the world of cancer precision medicine. This article, "Olaparib Monotherapy in Patients With Advanced Cancer and Germline BRCA-1/2 Mutation,"[1] was published in the January 20, 2015, issue of the Journal of Clinical Oncology.

It is well recognized that olaparib, a PARP (poly ADP-ribose polymerase) inhibitor, is active as a single agent in ovarian cancer. This drug was recently approved by the US Food and Drug Administration for noninvestigative use in the clinical setting of patients who have already received therapy for ovarian cancer.

In this particular study, however, the researchers treated a large number of patients—the sample size was approximately 300—who had BRCA1 and BRCA2 mutations that went across tumor lines. Not surprisingly, in this population of patients, the observed objective response rate was about 30%, with an overall response rate of about 25%, in the entire population of women with these mutations.

Most notable, in my opinion, was that in the patient population with BRCA1 or BRCA2 mutations and pancreatic cancer, which included patients who had not responded to gemcitabine, 5 of 23 patients, or 22%, achieved an objective response. In a much smaller patient population with prostate cancer for whom standard therapy failed, 50% (4 of 8 patients), achieved an objective response.

Compelling, Important Findings

This is incredibly important, provocative data in the setting of a drug that has been used in one tumor type being used for a particular well-recognized mutation seen in another tumor type. That 22% level of response is surprising and important, considering the anticipated response related to second-, third-, and fourth-line chemotherapy would be very modest, at best.

This is a wonderful example of the future of cancer precision medicine. The molecular alterations were identified using a drug that has been approved for another purpose, and the use of this drug in this setting has potentially achieved major clinical benefits. Clearly, any time you see a report like this, you want it to be confirmed by other investigators. But the rationale for the use of olaparib in these particular settings is well established, and now I believe that we have very strong clinical evidence to support the use of this drug in these very specific clinical settings.

If you are interested in this area and in the future of precision medicine in cancer management, I encourage you to read this very provocative paper in the Journal of Clinical Oncology. I thank you for your attention.


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