Would you consider off label use of olaparib maintenance in patients with somatic BRCA1 mutated pancreatic adenocarcinoma?

In addition to the comments above, it is worth observing that preliminary prospective data addressing this question was presented at AACR this year by @Dr. First Last. Her group is evaluating the role of rucaparib maintenance for patients with either germline or somatic BRCA or PALB2 mutations. Of the 19 patients presented in this interim analysis, one of the responding patients harbored a somatic BRCA2 mutation. Hopefully, we will continue to accumulate data on the appropriateness of PARPi maintenance in the small subgroup of PDAC patients with somatic, not germline DNA damage response genes. 

I have been using olaparib as an off-label maintenance strategy for patients with germline mutations in dsDNA repair proteins. And, as a side-note, we have an ongoing trial at DFCI for niraparib for patients with germline or somatic alterations in dsDNA repair genes that extend beyond just BRCA1/2.

This is a wonderful opportunity to discontinue FOLFIRINOX in a responding patient before accumulation of significant peripheral neuropathy. Should he/she fail to benefit, your patient has gained a holiday from FOLFIRINOX and can resume therapy.  But you buy your patient the chance for durable disease control absent multiagent cytotoxic chemotherapy.  And ultimately, you can't wait.  There is compelling data that olaparib is not effective in gBRCA patients after prior progression on a platinum. So by waiting until FOLFIRINOX is no longer effective, you are also waiting until olaparib will not be effective either. 

A brief anecdote from the POLO trial. I enrolled multiple patients on this trial, but one patient stands out to me.  The patient had a germline BRCA2 mutation and had a dramatic response to FOLFIRINOX. I enrolled on POLO (Olaparib vs placebo) and she had a progression after 4-months. I then re-exposed to FOLFIRINOX x 3-months followed by 5FU/Onivyde x 3-months (after neuropathy) with another profound response. I contacted AZ and the POLO trial and asked that she be un-blinded. She had received placebo during first exposure. I wrote for off-label olaparib and she has remained with a near-CR for ~2-years. So when you look at the survival curves in NEJM, she is on the placebo arm and is one of the long-term survivors - but that is only because she went on to receive olaparib.  She feels wonderfully and I still have FOLFIRINOX and Gem/Abraxane in my "back pocket" for when (and if) she ultimately progresses.

Definitely yes. However, it is infrequent to find a situation where one would stop FOLFIRINOX if the patient continues to respond. More likely, would use in situation where a patient would require a treatment break because of toxicity. Previously, would increase interval between treatments.