Pancreatic Cancer spread to the liver: What's next?

I was the first patient in the US that enrolled in the RucaPANC trial for targeted therapy in metastatic pancreatic cancer patients possessing a germline or somatic BCRA1, 2 or PALB2 mutation. I had a two week pause after finishing Folfirinox while it was still showing efficacy. I had a complete response to the PARP inhibitor Rubraca (Rucaparib) and now the longest patient in the world on this PARP inhibitor. I was in the trial from October 2014 until it was terminated in April 2016 and continued on the drug under compassionate need status. I am followed long term every six weeks and have been NED since at least 2016 and an 11.5 year survivor of metastatic disease to the liver of which there is no trace today.

The top two experts on BRCA in pancreatic cancer patients are Kim Reiss-Binder at the Abramson Cancer Center of the Hospital of the University of Pennsylvania (PennMedicine) and Eileen O’Reilly of MSKCC. I would contact those two for opinions in doing maintenance monotherapy with a PARP inhibitor such as Olaparib (Lynparza).

One day at a time, best we can do

Is the clinical trial targeted ro your particular gene mutation?

I too have been recommended for radiation at a resection site in my liver. However, knowing it can only be done once in an area I am reaching out for second opinions. I will finish my cycle of Gem/abraxane this week. Always get second opinions! My great surgeon architected a strategy that has kept me working full time since my stage 4 diagnosis 11-2021.
Nonetheless, I am hoping to meet with someone at Honor Health Institute and also John’s Hopkins soon in hopes there is a clinical trial appropriate.
There are various opinions on radiation .

Go for it! Will be rooting for you as you move forward

Why did they terminated it? It seemed like a good therapy.

Clovis Oncology filed for bankruptcy on 12/11/2022 and assets of the company were liquidated in March 2023 with Pharma and Schweiz GmbH-a holding company in Zug, Switzerland acquiring the marketing rights as well as the right to do further development if they choose.

AstraZeneca has a commanding lead for PARP inhibitor use in ovarian, breast and pancreatic cancer. Clovis Oncology saw that they would never get a return on investment doing further development of Rubraca so they focused on getting FDA approval for,breast cancer. That did not happen and with nothing to attract an infusion of cash to further development efforts, bankruptcy resulted.

Rubraca is made available to all those that were receiving it on compassionate use from clinical trial success as well as those that are able to receive it on Rx for ovarian and prostate cancers driven by a BRCA mutation.

Hello,
I was diagnosed stage IV with large Mets in liver 11/2021. With aggressive treatment at a pancreas center of excellence I am still here and doing all the things I love, including work.
Don’t get caught up in labels! But do get on the right chemo for you and consistently advocate for yourself. Unless you are in a center of excellence, many doctors just are not tied in to research and “out of box” thinking for their patients. Show them you are strong and an attitude of excitement about life. Doctors want success stories, they need us!!!

I tried to get olaparib on a compassionate basis in australia and AstraZeneca said no. It is available at an affordable price if you have ovarian and some form of prostate cancer but not pancreatic.

@stageivsurvivor is PARP present in everyone that has cancer or is that a specific one that shows up on next generation sequencing? Wondering if this is a specific or more general targeted mutation. Thank you!

I'll offer a short, quick answer based on what I know, and let the expert follow up and clarify when available and correct if necessary. 🙂

PARP itself is a protein in your body rather than a mutation that would show up in NGS.

Like all living cells, tumor cells need reliable duplication of their DNA in order to reproduce. Some cells suffer DNA damage (some just statistically, some as a result of chemo, radiation, etc), but have some inherent self-repair mechanisms that restore normal replication (and uncontrolled growth).

There are various "pathways" involved in "DNA Damage Response (DDR)" and PARP is used by the cancer cells in some of those. In particular, patients with certain mutations (BRCA1, BRCA2, PALB) that do show up on NGS benefit from inhibiting PARP from contributing to the repair process and (hopefully) causing the cell population to decline and die off.

The ATM mutation is similar in having a targetable impact on DDR, but relies on a different pathway (ATM/ATR), and thus requires a different class of drug (ATR inhibitors) to achieve similar effect. There are at least 2 ATR inhibitors in clinical trials now, but none approved that I know of, and thus not available outside of a trial.

Olaparib (a PARPi) is approved for treatment of several cancers, and can thus be used "off-label" in other cancers when appropriate. In PC, it is approved for patients with the three aforementioned mutations (BRCA1, BRCA2, PALB). It could be tried off-label in PC patients with DDR-related mutations (like ATM) but there is not yet any strong enough evidence to support it.