No Stone Unturned – Connor’s Pancreatic Cancer Journey

Thursday, September 19, 2024

We are grateful to be sharing the lived experience of Connor and Jen who have documented their personal journey with pancreatic cancer up until Connor’s passing in October 2024, to help other families cope with the challenges of this disease. 

For Connor, the genetic tests showed a few different mutations, the most promising of which included:

ATM mutation (germline) – this mutation did not show up in the tumour tissue, it was inherited from Connor’s dad, who also had cancer. 

KRAS mutation (somatic) – This mutation is in 90%+ of pancreatic cancers, and by the time that Connor was diagnosed, it was well studied with little progress, but there was more promising research ongoing in 2022 and our oncologist felt at that time that the researchers may be on the cusp of something and she described this as the “holy grail of pancreatic cancer,” if a targeted treatment can be discovered.  Note – she was right that they were onto something! 

FGFR1 amplification (somatic) – This isn’t seen very often in pancreatic cancers, but it is in other cancers and there are drugs that target these types of mutations.  Although further down the line of priorities, it still offered an option. 

What the results meant for Connor… 

Even before we considered a clinical trial, these genetic results helped to provide some information on how Connor may respond to chemotherapy, radiation as well as what existing targeted treatments could benefit him.  

The ATM mutation is in a similar family to the BRCA 1 / 2 mutations and increases your risk of developing certain types of cancer when inherited.  It also makes you more responsive to some treatments.  For example, people with an ATM mutation often respond well to platinum based chemotherapy drugs, like Oxaliplatin.  We know now that this was the case for Connor as he spent a year on Folfirinox, with good disease control and a partial response.  Some people with the ATM mutation also respond well to the PARP Inhibitor Olaparib (Lynparza).  This is an oral targeted treatment with far fewer side effects than chemo and no need to go into the hospital for systemic therapy.  Connor spent three months on Olaparib before his disease progressed.  Those with an ATM mutation also often respond well to radiation, which Connor has just started to receive for the management of bleeding and pain in August and September 2024.  

(We will talk more about clinical trial options soon.)

What the results meant for our children…

The other benefit of getting the inherited genetic testing was to understand the impact for our children. In 2022, our children were 2 and 4 and because cancers associated with the ATM mutation are very rare in children, they have not undergone any testing. We are hopeful there will be a cure for cancer by the time they would need to be screened.  Either way, we know early genetic testing and screening will be a priority when they are older. 

Secondly, if both parents have an ATM mutation the children are at a high risk for developing a disease called Ataxia-telangiectasia (A-T) syndrome which is a rare neurodegenerative syndrome.  A-T causes movement issues in children, often starting in pre-school and increasing in severity over time.  It also significantly increases the risk of certain childhood cancers.  The genetic counsellor recommended that I get tested as well to see if our children were at risk for this syndrome.  Fortunately, the testing showed that I did not have this mutation – although testing is never perfect, this gave us a lot of comfort.

By the summer of 2023 there were some very promising clinical trials targeting KRAS – a mutation commonly seen in pancreatic cancer (> 90% of the time) as well as non-small cell lung cancer. For almost thirty years, this mutation was thought to be undruggable, meaning they couldn’t find a treatment that could get at it. These are early phase (phase 1 means first in humans), and they are focused on figuring out the right dose (the highest dose that can be given without having unmanageable side effects).

One of these trials seemed incredibly promising both to our oncologist and from our own research. The phase 1 trial for RMC 6236, a PAN KRAS inhibitor, was new and in high demand. Trials for this drug were only available at approximately 10 medical institutions in the summer of 2023, all of which were in the US. We took the approach of contacting most of the institutions to get on the waitlists – some would add Connor to the waitlist prior to an appointment, others with a virtual appointment and some required in person visits. We also realized most would put Connor on the wait list BEFORE he progressed on Folfirinox. Had we known, we would have started our outreach earlier.

RMC 6236 in Cincinnati

On September 12, 2023, Connor got a call from Christ Hospital in Cincinnati that a spot had become available on the RMC-6236 trial. At this point, Connor’s treatment history looked like this:

• Folfirinox (Standard of Care – 1st Line) – May 2022 – January 2023 (16 rounds)
• Olaparib (Maintenance) – February 2023 – April 2023
• Folfirinox (Standard of Care – 1st Line) – May 2023 – July 2023 (6 rounds)
• Gemcitabine Nab Paclitaxel (Standard of Care – 2nd Line) (4 rounds, no progression, but got a spot on KRAS trial)

This seems like a lot of treatment, but our oncologist had made very wise decisions and Connor was able to go back to Folfirinox after Olaparib to get as much mileage as possible. We also spent a lot of time discussing whether to go on a clinical trial when Connor had not progressed yet on Gemcitabine Nab Paclitaxel – would it still work if he went back onto it later? After much thought and many opinions, we decided the clinical trial was just too good to say no to. We had also spent a lot of time doing everything we could to get on waitlists and were on about six. We expected the earliest a spot would come available was October, but more likely November/December, so we were ecstatic when he received the call.

In order to be a part of the clinical trial, many tests had to be done (EKG, ECG, CT scan, x-ray, bloodwork, physical, etc.). All of this had to be done on site at the trial location. In addition, you needed a three week wash out period from your last chemotherapy dose. Connor’s next chemo was quickly cancelled, and we began making plans to go down to Cincinnati for the screening.

Because all test related procedures/monitoring needs to take place at the trial site, Connor had to spend several days in Cincinnati, so we decided to make the most of a week away and brought the kids to Cincinnati. 

We had several good months while Connor was on the trial drug – like doing F45 good, feeling the most like himself he had since the diagnosis. Well worth the effort for an incredibly memorable period of time. 

Unfortunately, by March 2024, it came time to pivot treatments. With gradually increasing symptoms since January and rising tumour markers, Connor was concerned that the trial drug wasn’t working as well. Although his January scans were stable, his scans in March showed subtle changes.  When combined with how he was feeling, the trial team concluded that the disease was progressing, and it was time to come off the trial drug.  As ever, Connor was very in tune with his body and felt it was like the right decision.   

We are incredibly grateful that we had the opportunity to participate in this trial. With every bit of hope we gained, we also know there are still patients out there who don’t get the opportunity to try some of the cutting-edge treatments (due to late diagnosis, ineffective chemo, lack of access, etc.).  We hope to be able to take what we’ve learned and do our part to help support others.   

Additionally, because of the smart decisions by his oncologists, Connor was able to go back to the Gemcitabine Nab Paclitaxel for a short period after the trial and to this day, his journey continues. 

Read more from Connor and Jen