Parp Inhibitor Use for subsequent remission

Deletedbyrequest

I am just wondering if anyone used a parp inhibitor after remission; then had a first recurrance; then used a parp inhibitor for the second time.  Or if you were switched to a different maintenance drug ?

Strongwoman

@Cecile21
  That is a good question.  I am positive one of the ladies that have utilized the PARP Inhibitors will get back to you shortly on this.  
  I will look forward to reading about it when it gets posted.

Fearless_Moderator

@Cecile21 Good question.  I was on Olaparib for almost 2 years to treat my first recurrence but for me it was a controlled clinical trial.  That said, after I recurred again and went through chemo I was told I couldn't qualify for a PARP for maintenance since it had run its course with me.  I'm not sure if it's a medical decision or related to the criteria the Ontario MOH requires they follow to have the drug qualify for use.  I can say I can't recall a single post here where anyone mentions they we able to switch drugs. There may be some, now that some of the PARPs have been more formally approved for use who have received it after a subsequent recurrence again but also can't recall anyone mentioning that.  

If you haven't already, I'd suggest you ask your oncologist, especially if you're lucky enough to have one that 's a medical oncologist,  Like Strongwoman I'd be interested to see if you get any replies or your research turns up any information on the topic.  Thanks for raising it.

GloHo

@Cecile21

I find myself heading in that direction right now.

Diagnosis #1...chemo (6 treatments)...2 1/2 years NED...Recurrence #1...chemo (11 treatments)...Zejula (2 months)...CA125 increased quite a bit and CT showed progression

I have an appointment with my Dr. on Monday. The plan is back to chemo -  with carbo (weekly) + Caelyx or Bevacizumab (bi-weekly), followed by maintenance with either Caelyx or Bev. Will be confirmed on Monday.

I was going to ask if I could go back on Zejula or not because I've seen some posts where Zejula + Bev have been used for maintenance.

Will keep you updated.

Deletedbyrequest

With regard to chemo, then Zejula, then recurrance.  First to note that even with recurrance as defined by CT, my CA125 has not gone above 20. My oncologist does not seem to think that Zejula would be of any use for me ( my first remission was 2 years HGSOC with Zejula) as he believes that it is now not effective. HOWEVER my understanding is that Windsor is not a main centre for reproductive cancers. I was diagnosed in Mississauga and referred to London where I had my debulking surgery done. My referral to Windsor was for Chemo, since it was only 30 mins from home as opposed to 2 hrs. I have questioned my oncologist about this and he indicated that he would contact a colleague. I am sttage IV so I would hope that there is some sort of maintenance therapy for me. 

Fearless_Moderator

@Cecile21 I know how confusing it can be getting transfered to a satellite and the lack of specific expertise you encounter at them.  With all due respect chemo is chemo and the expertise would be there for that purpose but beyond that I would ask for a referral to a \Medical Oncologist at a Regional Cancer centre (that may be Juravinski in Hamilton) to discuss options that might be available to you to slow down or stop progression of the disease.  It's just a consult to weigh options so no one should be offended about the ask.  Good luck. Hoping you'll get some answers. 

GloHo

@Cecile21

Hi again. Sorry for the delay. I feel like I've been taking one step forward and then careening two steps back lately!! My oncologist retired and I had an interim Dr, my new oncologist has just started and things are now moving forward!!

Was on Zejula for two months following my second round of carbo+taxol. Zejula didn't work and CT showed my cancer has progressed. Since my recurrence was under 6 months, I am now considered platinum-resistant. (I am BRCA-negative.) 

My new course of action is Caelyx + Avistan (Bevacizumab). Avistan every two weeks + Caelyx every 28 days. A return to Zejula alone and/or with another drug was not an option. 

@Fearless_Moderator makes a good point about reaching out to a Medical Oncologist to determine what options are available and the best fit for you. 

I have also advised my oncologist that I would be interested in a clinical trial. Not sure how all that works, but I have been looking at some info available online but haven't done a deep dive into the specific trials yet.

Keep us posted.

 

ellie

Hi,
Joining in on this conversation but late.  Research supports low efficacy for PARP inhibitors on recurrence.  And research indicates that Overall Survival can be reduced by taking PARP inhibitors after recurrence.  In considering any research, one has to keep in mind that PARP research tends to channel HGSOC participants into groups of BCRA+/HRD positive (couple of groups) and BCRA negative/HRD negative.  Participants in the first 2 groups have better outcomes than HGSOC participants in the latter group who--and I am in that latter group.  I am still in NRD status and taking a PARP inhibitor but am not sure if indeed it is helping.  Time will tell.

GloHo

@ellie
Interesting info for sure! Thanks for sharing and good luck on your maintenance treatment with PARP! 🤞

CrazyCat

@ellie
Your comment regarding the research caught my eye and I wonder if you've heard it from your oncologist.  I found the same information on-line and questioned my oncologist about it.  His response was that the math used in the study was flawed, and that they now do not believe use of PARP after a recurrence reduces Overall Survival.  I sure hope he is right, as I am on Zejula following treatment with carbo for my first recurrence.  

ellie

Hi CrazyCat

At this point you need not worry--the decrement to OS seems to be associated with recurrent OV and then PARP treatment.  But it also is associated with non-BRCA mutations with HRD negative.  Where are you with either of these DNA/gene characteristics?

Re your comment from your oncologist: I read the research paper (on ENGOT-OV16/NOVA) and my oncologist substantiated that evidence on niraparib re OS versus PFS is not clear; PFS may be extended but OS may be less.  The paper suggests flaws as your oncologist may have noted: 'Although the study was not powered for OS, was performed at a one-sided a-level of 0.025, and interpretation of OS is confounded by a high rate of crossover and missing data, these results warrant caution.' This is supported in the 'ASCO Guideline Rapid Recommendation Update' published August 30, 2022.  It appears that the ASCO guidelines are well-scrutinized re supporting research. The recommendations state: 

Recommendation 3.0. PARPi monotherapy maintenance (second-line or more) may be offered to patients with EOC

who have not already received a PARPi and who have responded to platinum-based therapy regardless of BRCA

mutation status; treatment is continued until progression of disease or toxicity despite dose reductions and best supportive care. Options include olaparib 300 mg every 12 hours, rucaparib 600 mg every 12 hours or niraparib

200-300 mg once daily. (Type: Evidence-based, benefits outweigh harms; Evidence quality: High; Strength of recommendation: Strong.) Maintenance treatment with niraparib for patients without germline or somatic BRCA

mutation should weigh potential PFS benefit against possible OS decrement. (Type: Evidence-based, benefits

outweigh harms; Evidence quality: Low; Strength of recommendation: Moderate.)

Recommendations 3.1/3.2. PARPi monotherapy should not be routinely offered to patients for the treatment of recurrent platinum sensitive EOC. (Type: Evidence-based, benefits outweigh harms; Evidence quality: Intermediate; Strength of recommendation: Moderate.) Evidence on PARPi use in this setting is evolving and data are continuing to emerge.  Any decision to proceed with PARPi treatment in select populations (BRCA mutation, No prior PARPi use, Platinum Sensitive, Advanced Lines of Treatment) should be based on individualized patient and provider assessment of risks, benefits, and preferences.

Hope this is helpful.

CrazyCat

Thanks for all of this info @ellie!! Looks like you have done more reading on this than I have. I do not have a genetic mutation. My new oncologist has sent a tumour sample for testing as he thinks it highly likely that I have a somatic mutation. He sent it November 8 and I’m still awaiting results. He felt it was still a good option for me but results would be better if I have a mutation. 

ellie

CrazyCat,
I am surprised that your original tumor(s) pathology report did not state either a BRCA Germline (that is, inherited) or BRCA somatic.  It usually does--but then different hospitals pathology dept. may provide less info.

The other mutation that is relevant to poor DNA repair is the HRD designation.  It means cell repair does not involve double strand repair.  If you have HRD or BRCA mutations, then PARP inhibitors will do more than if you are HRD negative (that is, DNA repair is double strand).  HRD testing is done thru Myriad and in the US.  Your hospital has to authorize that test to be done.  But it is important!!!  You are  in the 50% of better prognosis.

Just some thoughts.
 

CrazyCat

Ellid,
 I wasn't aware that they could test the tumour for the hereditary mutations.  Through Hereditary Cance, I had blood work done after or during chemo to test for that.  I was told I qualified because of the type of OC I have.  It took quite a while to get the results. They also counselled me to consider it carefully due to the family ramifications.  I was conflicted on whether to be happy or sad with the negative results.  On one hand, I was happy that it was not in my family, so didn't need to worry about family members, and on the other hand, I was sad to not qualify for Olaparib.   Yes, different hospital pathology dept. may provide different information, and/or perhaps some of it is tied to provincial funding??? I know that my new oncologist was sending a tumour sample away somewhere to be tested,  He referred to it as an oncopanel.  I don't know where that would be done, but I assumed not locally.  I wonder if, due to research developments, this has become more relavent now than it was in 2018 when my original pathology was done.  

As an aside, the oncologist I had when I began my recurrence chemo in July 2022 would not even talk to me about maintenance with PARP inhibitors.  She said we'd look into it when I completed chemo. I can see now that she was not up-to-date with how it's handled in BC, as my PARP treatment had to begin within 12 weeks of completing chemo in order to be funded.  Fortunately for me, she was a locum who returned to the UK part way through my chemo and just before she was going to add Caelyx to the mix and add at least one extra cycle.  This decision was in conflict with what she told me at the outset, that if carbo alone was smashing my numbers, which it was, then we could stay with just carbo.  My new oncologist felt quite differently from her and so consulted with their colleagues.  They agreed with him, that I very clearly did not need either Caelyx or extra cycles.  My CA125 was in the normal range after 2 treatments of carbo!!  He immediately sent off the tumour for testing, and said he wanted to put me on Zejula. 
I think someone is watching out for me!!!

I also think that there is a lesson here for all of us - don't be afraid to seek a second opinion!

Strongwoman

All I can say is WOW to the ladies with HGSC. I have been following your thread and compared to LGSC it is very involved. I found some difficulties in fielding some of the posts while @Fearless_Moderator was navigating her journey.
 With LGSC our choices are surgery, chemo, Letrozole and Trametinib. Possibly radiation if any tumours are big enough and is safe to the surrounding structures. That is it.
  The myriad of possibilities with tumour markers themselves let alone treatment options is staggering for HGSC.  My hat goes off to all navigating your journey through it. It seems like a lot of balls up in the air all at once.
 Soldier on all of you!

ellie

Thank you for that Strongwoman.  HGSOC is hugely complex.  Unfortunately.  Simpler but still not straightforward if one falls into the BRCA, HRD, RAD51 plus a couple of other gene mutations.

I have none of those.  I fall into the 50% of HGSOC that is challenged.  I hope that clinical trials will unearth more possibilities for this group....

I am blessed to be with the Princess Margaret Cancer Centre and I live about a 20 minute walk from it.  

ellie

And I am also blessed that my diagnosis was in 2022 and not earlier, as CrazyCat pointed out re 2018 practices and knowledge.  I am convinced that whomever is diagnosed with HGSOC in 2027 will have many alternate paths to longevity...and that a screening test for early detection will be a standard and affordable practice.  For any type of OC. Let's hope.   

CrazyCat

Ellie, sorry I misspelled your name last time. 
You make an important point that things are finally looking better for ovarian cancer patients.  The future does indeed look brighter.  Vaccines are looking promising, though looks like they are at least 5 years out.  Just hope we all live to see the improvements!!

I am rather curious re the differences between provinces.  I have a feeling Ontario may be offering more than others.  So many decisions are tied to available provincial funding.  

ellie

Yes, you are so right re provincial funding.  The visibility and strength of the oncologists/hospital play into that funding.  I worry about BC when I see articles on cancer patients having to wait to see oncologists or get treatment.  I have experienced some delays at times here due to constraints on resources.  But realize that triage is real in our system and provincial barriers cause problems with transparency and cooperation cross borders.

melissa

Recently diagnosed in June with stage 3B Clear cell, surgery in July cytoreduction hysterectomy with bilateral salpingo opherectomy and omentectomy. There was no visible intra abdominal disease, only tiny spots on omentum. Just had round 3 of carboplatin/taxol but am quite anxious about all I'm reading in regards to clear cell being much less chemosensitive. Waiting to hear back from my oncologist as she mentioned immunotherapy. Any other clear cell ladies out there?

Strongwoman

Hi @melissa.  Welcome to the group.  I do not have that type but went digging for some info that is as current as of March 2023.  Here is the link to what I found New therapies for clear cell ovarian carcinoma - PubMed (nih.gov)
  In it, it does say that when you receive chemo for it, it is not as effective. This is much like low grade serous (LGSC).  In the article it does state that there seems to be clinical trials for it or they are working on some.  Here is the link to Ovarian Cancer Canada (OCC) Ovarian Cancer Clinical Trials | Ovarian Cancer Canada (ovariancanada.org)
If you can't find what you are looking for, call or email them to see if you can get a clearer picture.  I hope this helps.
  If it is of any help to you, us LGSC gals don't have many options either. It is a difficult place to be and it is a lot to process.  I do hope that OCC has some leads for you and that you have much success.
  Drop another post sometime to let us know how you made out and it may also help other Teal  Sisters out there or in the future.
Take care