Should PARP Inhibitors Have Tumor-Agnostic Approval Status?

Maurie Markman, MD


August 19, 2019

This transcript has been edited for clarity.

Hello. I'm Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia.

I want to discuss a very important paper[1] that recently appeared in the New England Journal of Medicine, entitled "Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer." This paper was also presented in a plenary session at this year's American Society of Clinical Oncology annual meeting.

This randomized, placebo-controlled, double-blinded study revealed that patients with metastatic pancreatic cancer who received maintenance olaparib vs placebo doubled their median time to disease progression—7.4 months vs 3.8 months—and after 2 years, the percentage of patients without disease progression essentially doubled [22.1% vs 9.6%]. I hope this will lead to the approval of olaparib as a maintenance treatment strategy in patients with BRCA-mutated metastatic pancreatic cancer by the US Food and Drug Administration (FDA). Roughly [4%-7%] of patients with pancreatic cancer will have a germline mutation.[1]

We have strong data for the benefits of poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors. But do we have enough data on PARP inhibitors and their benefits in metastatic cancers in the presence of germline BRCA mutations to seriously consider a tumor-agnostic approval for their use in the maintenance setting in patients with metastatic disease who have achieved response to chemotherapy? Various PARP inhibitors have been used in ovarian cancer, breast cancer, and now pancreatic cancer.

Do we have to look for approvals by specific tumor type when we know that BRCA mutations may occur in 1%-[5%][2] of patients? It would not be possible to conduct randomized trials in these disease settings. And yet, in my opinion, we have overwhelming data supporting the benefits of BRCA mutations as driver mutations that are impacted by PARP inhibitors.

Is it time for the FDA to seriously consider tumor-agnostic approval for PARP inhibitors—one or more, depending upon the data that are available—for the use of these agents as a maintenance strategy in metastatic cancers that will lengthen time to disease progression and likely improve overall survival? This is a very important and provocative question.

I encourage all to read this important paper in the New England Journal of Medicine. And for those of you who are not familiar with the data in breast and ovarian cancer, read that as well to consider this question.

Thank you for your attention.

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