Questions about maintenance chemotherapy

Hoping to hear details on this as well. The POLO trial cited in this article https://ascopubs.org/doi/full/10.1200/EDBK_397082 says Olaparib/Lynparza was approved in 2019 for maintenance therapy for patients with BRCA1/2 and PALB2 mutations. ATM is similar to them in terms of DNA Damage Repair, but not sure if an oncologist can prescribe it for ATM or get insurance to cover it. If not, I think there are other clinical trials going on with Lynparza that you could get into with free treatment (as long as you don't get randomized to placebo).

Dr. Eileen O'Reilly at MSKCC was particularly interested in this; would be awesome if your oncologist could touch base w/ her and see where things stand, what options there are, etc. MD Anderson (research Dr. Timothy Yap in particular) is involved in several other clinical trials related to ATM mutations, but might require regular travel to Houston. MDA (and several other sites) are participating in a new CAR T-cell trial called BASECAMP/EVEREST; you should get tested to see if you qualify for that one. MDA is also about to open a trial using NK CAR cells. Both of these are one-time treatments, so travel is minimal.

I'm getting a much better response to Gemcitabine+Abraxane+Cisplatin than I did with mFolfirinox. Not sure if that's related to ATM mutation, some other trait, or simple coincidence. Dr. O'Reilly points out in other papers and videos that there's a sweet spot (known for the BRCA1/2 & PALB2 patients) for switching to PARP inhibitors like Lynparza after ~16 weeks of stable disease on platinum-based treatments. After developing resistance to platinum, disease often becomes resistant to PARP inhibitors as well.

Hope you'll post anything you learn about this as well. Thanks and best wishes!

@ncteacher, in addition to @markymarkfl's helpful information, I think that fellow members like @russelltturner @asingh90 @stageivsurvivor @pendesk8 may have additional experiences to share related to ATM genetic mutations, maintenance therapy options like Lynparza (olaparib).

Have you and your care team made a decision?

I have the (g)BRCA2 mutation and was the first patient accepted into the RucaPANC clinical trial conducted at the Abramson Cancer Center of the Hospital of the University of Pennsylvania from 2014-2016. That clinical trial was open to BRCA1, BRCA2 and PALB2 germline and somatic mutations. I did 24 cycles of Folfirinox for metastatic pancreatic cancer to the liver to get maximum benefit out of it before doing maintenance monotherapy using the biosimilar drug to Olaparib (Lynparza) called Rucaparib (brand name Rubraca).

I have been on the PARP almost nine years. I had full dose until exactly six years on it when I began to feel the effects of anemia and did one dosage reduction. Rubraca was approved for ovarian, breast and prostate. The original developer Clovis Oncology did not apply for FDA approval. AstraZeneca with Lynparza beat them to a very small market and Clovis had limited financial resources that they were using to get approval for treating breast cancer. Clovis filed for bankruptcy December 2022 and the Rubraca asset was purchased by Pharma and Schweiz with offices in Austria and Switzerland. The drug is manufactured in Switzerland as it is prescribed for the FDA approved uses. Those that participated in clinical trials for pancreatic cancer are using it under compassionate use and obtain it at no cost.

The expert at Abramson Cancer Institute with PARP inhibitors is Dr. Kim Reiss-Binder. She has conducted trials of both Rubraca and Lynparza. She is the PI of the Apollo trial EA2192 that does not include ATM mutations.

On this topic, has anyone discovered maintenance therapy options, trials or advanced research for KRAS G12D mutation?

Colleen, thanks for your post and for pulling this thread higher in the list! And @stageivsurvivor , thanks for your reply as well. As your post indicates, there isn't much definitive for ATM-linked cancers at this point. I'm also nowhere near the UPenn cancer center.

So far, we haven't made a decision on which way to go re maintenance. I just had chemo no. 7 on Monday 8/21 after that lengthy gallbladder-related layoff, and I'll have round no. 8 on Tuesday 9/5. Scans have been scheduled for after that, and I'll see the oncologist on 9/14. Right now, though, I'm inclined to go with the Folfiri approach rather than olaparib (Lynparza). It appears that Folfiri has a better, longer success rate at holding off progression than olaparib. Meanwhile, I'm tolerating the reduced-dose Folfirinox well and my CA 19-9 continues to drop. The Folfiri maintenance would be the same dosage level (60%) and same frequency (every 2 weeks).

Adding to the consideration, the NP said yesterday that it's possible I could continue on Folfirinox for a few more rounds as long as my numbers continue to drop and I don't experience increasing toxicity, such as neuropathy. There doesn't appear to be a "magic" CA 19-9 reading at which you'd switch from active treatment to maintenance. She said scans would be a better indicator, and that makes sense. We were intrigued to note that the NP distinguished between neuropathy and cold sensitivity. The cold sensitivity can be triggered by touching something cold, but isn't active the entire time; with neuropathy, you feel the nerve dysfunction constantly. (I swear my original oncologist didn't make that distinction.) I have cold sensitivity, but no neuropathy, which bodes well for continued treatment. Anyway, we'll see how things play out during the next few weeks.

Thanks for the very detailed response. I will be starting with Olaparib. I have BRCA1. I am concerned about the potential side effects but determined to give it a try.

This article
https://letswinpc.org/research/targeting-the-undruggable-kras-protein/
mentions this study
https://classic.clinicaltrials.gov/ct2/show/NCT03608631
at MD Anderson
"iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation"

I'm not sure of the study status or if you already knew about, but it might be something to follow up on. Hope it helps somehow. MD Anderson has a lot of good stuff going on!

I'm glad to hear you have had positive results from your treatments. That must have be awful to have gallbladder surgery inbetween your treatments too. I seem to recall my doctor told me I had the ATM mutation when I had my biopsy & genetic test of my tumor. I was told in October there wasn't any targeted treatment for the ATM mutation at the time. I was also supposed to go on maintenance chemo too but my cancer markers have started to rise now that I'm on G-A. I'm really happy for you. Hope things continue in the right direction. Take care.

@margefromwi , have you asked your oncologist about adding Cisplatin to the GA mix? The ATM mutation is supposed to respond well to platinum agents, and the 3-drug combo has brought my CA19-9 down by about 95% (for now).

If that doesn't help, MD Anderson in Houston has several clinical trials going on that ATM mutants like us are eligible for.

Thank you for the information! I will pass this on to my oncologist. Take care!