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Hi,
I am posting this to encourage those who fall into the HGSOC with BRCA negative and no HRD to respond.  I would like to hear your stories.  My reason for this post is to learn what others with this type of OV are experiencing. While HGSOC is the most prevalent form of OV, approximately 50% of HGSOC patients are BRCA positive and/or are HRD positive.  These patients have the best prognosis of all of us with survival rates upwards from 50% at 5 years.  Much research focuses on improving that 50% prognosis for BRCA positive/HRD positive.  Hopeful survival stories for HGSOC patients usually reveal a BRCA positive/HRD positive or associated mutation background.  For example, a RAD51 mutation is linked to BRCA positive.

I am seeking stories from the other 50% of HGSOC patients.  I hope that some are hopeful, some will not be, but everyone's response helps me round out my view of our mutual challenge.  It is difficult to sort through others' stories when the 'cause' is different...our disease is incredibly complex so I find it helpful to narrow the field.

Hope to see others' stories.
Always hopeful.

@ellie I hope you get the responses you're expecting however it's important to note that while testing for the BRCA 1 and 2 gene has become pretty standard in most cancer centres, testing for HRD is generally only done when there is a necessity to know. My tumor tissue was tested for HRD 4 years ago when a positive was a requirement to participate in a specific clinical trial I had applied to join.  Otherwise I wouldn't know nor do any of my circle who have had only BRCA testing.  Fortunately the BioDiva study and other efforts to "bank" the genetic pool of survivors will help expose a better understanding of what is out there for both clinicians and patients.  

Understood Fearless Moderator.  And your remarks are valid.  While the HRD component may be unknown by many at this time, I hope that anyone with BRCA1 negative would respond.  I expect HRD testing will become more prevalent as it is important in many clinical trials.  PMCC does test for this now; it is one of those indicator tests when the sea of unknown mutations is broad and deep within the HGSOC domain.

@ellie I am BRCA 1 and 2 negative as well as negative for HRD. I paid to have it tested by a US lab (myriad) before starting Zejula as I thought it might help me make decisions around treatment if Zejula side effects were too difficult. I am negative for HRD as well. I did not have trouble with side effects except for rapid heartbeat but I recurred 6 weeks after starting which makes sense considering my negative status but very disappointing. I realized that I was no longer in the 'statistically more hopeful group' that responds to targeted therapy and it left me feeling vulnerable however I have been on weekly TaxolAvastin and responded very well and fast. Disease is still there but receded and most of my symptoms are gone. Not at all what I expected considering how aggressive it was in December and how much pain I was experiencing.   I have been given a treatment break to go on a delayed honeymoon to the UK and i"m active and mobile so I will enjoy myself. I I fully understand the emphasis on research and treatment for BRCA?HRD+. It's where they can make the greatest difference and in the end findings and treatment for BRCA/HRD + will expand. I guess it's important to know that even if targeted therapy is not for some of us, the old standbys are still working and we are living longer and better than in the past. Oh and I was also in the Bio Diva trial. No mutations out of the over 500+ except for TP53! I think this was the most disappointing. I wish they had found something. It would be something to go on at least. 

@mjmck21 @ellie
  Love reading your posts. I learn so much about options/trials/treatments in relation to HGSC.
  I don't have that type but LGSC and TP53 came up in my genetic testing as well.
  Looking forward to learning more as all with HGSC explore the variability of options for you all!

Thank you @mjmck21.  I am grateful...to have a colleague with similar challenges.  I do hope others respond who share our profile.  It is difficult to identify those with our profile in other OVDialogue discussions.

As you pointed out, research and treatment focusing on BRCA?/HRD+ makes sense.  Hearing some positive results using old standbys is encouraging.  Gives one hope where not much exists currently.  I believe that clinical trials involving T cells could eventually apply to ovarian cancer.  However, clinical trials are often focused on solid tumors associated with various organs--I assume that trial results are more obvious when the tumor(s) is simpler; eventually OC is tested for any recurrence benefit but often appears to be a year or 2 (or later) after the initial clinical trial.
  
TP53 seems to be present in many OC subtypes.  My pathology report also identified PAX8 and WT1.  PAX8 is frequently (maybe always) present in HGSOC; I am not sure about WT1.  PAX8 may be a promising target for clinical trials in HGSOC but the article I have was online in 2022; thus any clinical trials and benefit would be some years away.

I also have been on Zejula--since completing my first line chemo.  I am now experiencing a CA125 increasing trend so most likely, it is not working now.  I am waiting for results from a CT scan.  When I had to stop Zejula due to plummeting hemoglobin, I felt a lifeline had been cut, however short that lifeline was.

My hope is that others with our profile will engage and share.  Please share when you can @mjmck21.

Thank you @strongwoman and @ellie I should correct my use of term targeted therapy. I implied that I wasn't able to use targeted therapy but Avastin is considered targeted therapy so there is that. I was referring to the more recent therapies where bio markers indicated improved outcomes like PARP I. Anyway targeted therapy is a broader term. If I have this wrong please let me know.

Also I am unable to find the article now.... but I believe I read that Ottawa Hospital is considering expanding the application of CAR-T therapy beyond blood cancers and Ovarian might be one of them. This would be a ways off but to the point about T cells being the next development. The trial at PMH I was hoping participate in was for an immunotherapy treatment. I mentioned in other posts that I needed to have certain bio markers which I did not have, so was excluded from that trial but it is encouraging that immunotherapy is being considered for OC. I do not understand why immunotherapy has not worked for OC and have wondered but it turns out that the OCC research forum in June will address that very question so I will be looking forward to that. 

@mjmck21
I wish you a wonderful and trouble free delayed honeymoon to the UK!  Thanks for the heads up on the OCC research forum.  I do hope and expect that a recording will be available as I will be in the air at that time.  

Re immunotherapy, from what I have read, OC is characterized by a cold tumor immune microenvironment (TIM), whatever that means.  Seems like other cancer cells do not develop tumor-specific immune cells, as does OC.  I have read that OC turns Tcells into cancer cell supports which is frightening.  Love to learn more about all of this as it may provide some hope eventually.

hi all,

Thanks for this interesting discussion. I learn more here than in the Drs office.
I’m BRCA negative in germline test, ie it’s not hereditary. But my pathology shows loss of copy number for both BRCA1 and 2. The whole gene is gone in the tumours. If it’s homozygous, it could mean a good response to PARPi, but they were unable to tell from the test.
My HRD will only be tested now that I’m going on one of the PARP inhibitors. I’m not sure why it wouldn’t be tested earlier along with everything else.
I wish there was a flow chart so we could understand the reasoning behind these seemingly random decisions.

Hi @mcb and @mjmck21

Glad you found the discussion interesting. I have further comments on the PARP inhibitor and also an update.

It is now over a year since my last input to this discussion. I am sharing what this year has been like and perhaps offer hope to some of you. In May 2023, my CA125 had begun to rise…but to-date it has been fluctuating between 21 and 28. My lowest point was just after chemo when it was 17. I have been curious as to why the marker fluctuates so much (for me anyway) and find no answers. It just is. From my own experience, however, i have found a fluctuation above 28 twice: once when I had a horrible cold for 2 months Nov/Dec. 2023 (slowly increased to 30 over those months) and once more recently when I had a few hip/vertebrate problems and suffered with that for over a month. My marker jumped from 27 to 33…yikes! Thought for sure this was the beginning of recurrence. But no (said ecstatically), once I had been to my chiropractor about 4 times and the pain had disappeared, the marker went down to 28 and then a week ago, 25. Thank god. But both were examples of what inflammation elsewhere in your body can affect the marker. And there is no cancer (ct scan confirmed).

Another positive: I have now been on niraparib for almost 2 years, half dose. I do not know if the drug has been my savior, or if I was lucky and chemo worked miraculously in killing cancer cells. But there is hope…where i thought there was little. I will be on the drug for one more year. It has a few side effects still but they are MINOR.

I have met thru my PMCC visits, a couple of women who have been cancer free for 2.5 years while on niraparib. Hopeful. The downside is that at least 1 woman was suffering side effects that were severe.

I trust this is helpful and hopeful @mcb. The absence of BRAC1 or BRAC2 in your tumor may indicate that you have no mutation in those genes. If so, you would probably be prescribed niraparib rather than olaparib.

Hope your journey is positive, albeit stressful.

Hi @ellie

I’m encouraged by your response and you clarified the length of time on niraparib. I had read 2 years somewhere, but my oncologist said 3. I think she is leaning towards niraparib. In my case where the whole gene is just gone, it is similar to having a BRCA mutation. In either case the protein is mis formed or not made at all and cannot work as it should. Of course if it’s only missing on one allele and the other is normal then it’s no advantage.

Hi @mcb

Leaning towards niraparib means 3 years. If BRCA mutation is clear, then olaparib is prescribed for only 2 years. Don't know why the difference—have a cancer colleague who is on olaparib and have asked her…but she has not had a clear answer from her oncologist.

hi teal sisters,

I’m now 8 weeks post chemo and still waiting to hear about starting Niraparib. I know there is a 12 week window, but I don’t imagine the goal is to push the start date to the limit. Does anyone know where did that timeline came from? It seems rather arbitrary. If you started Niraparib, how long post chemo was a typical wait time?

Hi, @mcb

My wait was about 3 weeks. I do not want to worry you, but I believe if you are going to take it, that you must start now. I know my oncologist has taken me off the drug for a month maximum—and from her guidance and what I have read (research papers), a month is generally the 'allowable' time (if you need a break)…and I expect, from time chemo is complete to going on the drug. I am not sure where the 12 week window came from—I was not told that.

My advice is to push, push, push the oncologist to begin. You do not need the HRD results to begin. The drug can be effective if one is HRD positive or HRD negative. You have probable better outcomes with the drug if you are HRD positive.

Hope this helps.

Eleanor

hi @mcb - I started about 8 weeks post chemo. The guideline is within 12 weeks to allow time for your body to recover from chemo toxicities. I would encourage you to check in with your medical team to confirm your start date. You can access the regimen information at Cancer Care Ontario.
https://www.cancercareontario.ca/en/system/files_force/NIRP_GY_OV_P.pdf?download=1

@Sam373

Thank you for the link, it was quite helpful.

The insurance company approved coverage Dec 12 and the medication was delivered on Monday. I had to wait for my baseline appointment today though.
My care is managed at a regional centre but I am followed at a local satellite. Today I was just supposed to do labs and BP check. I asked when I was supposed to start taking the meds and there was a lot of confusion. It seems the documents sent to the satellite centre outlining the plan of care indicated that today is day 8 of cycle one. That’s impossible since I didn’t physically have the drugs until 3 days ago and hadn’t even had the baseline appointment. Why would the oncologist have indicated I started the drug on Dec 12? Then I read this in the Cancer Care Ontario document you linked to.

“To start within 12 weeks of completing chemotherapy.† † Disease progression should be excluded before starting niraparib, if > 8 weeks have elapsed from last chemotherapy treatment.

I left that appointment crying. I dont have confidence that my care is being managed properly. I will call the oncologist to get some answers when I’ve calmed down.

@mcb

I am so sorry that this process has been stressful for you. It’s frustrating to hear that they messed up the dates, but you are doing the right thing by continuing to ask about start date. From my own experience, there was some flexibility around start date and my oncologist didn’t mention that clause you read. The drug regimen is clinical information, but your medical team will treat you based on your individual case. I hope things get sorted out in the next couple of days and you’re able to start. Please keep us posted.

hi @mcb how are you doing? Did you get the answers you needed and have started the meds? I can only imagine how frustrating this has been. Thinking of you.

@Alwayslearning thanks for checking on me. I started Niraparib on the 19th. I haven’t spoken to the oncologist yet about why she entered the wrong data in my file. It seemed to have been hastily done because she listed the appointments for blood work but skipped 2 of them.
At least it’s sorted now. Hope you are well

Hi @mcb … I'm glad you got it started. I've noticed a few times that what's recorded in my medical records is not accurate and have spoken to the PA or Dr to have things updated. How are you doing on the Niraparib?