Her 2 climb with doxil (doxorubicin)

[Bunty]

Hi all,

I'm currently on Enhertu but may have to come off due to some complications.

There is discussion on Joining the HER2Climb with Doxil (Doxorubicin) trials in Australia.

Does anyone have any experience with this combination, e.g. real life feedback etc?

Thanks Marie

[Donna H]

I am also on Enhertu but have no experience with this trial. But I am interested to hear any comments. I had progression while on Enhertu, so my dose was increased and I had 10 radiation treatments. I'll get scans next month to see how all is going. My oncologist doesnt want me to stop Enhertu as there isnt a great alternative at present time.

[Nguyen]

>I'm currently on Enhertu but may have to come off due to some complications.

What are your complications with Enhertu?

Which her2climb trial, there are her2climb1-5. Regardless I don't see a her2climb trial with Doxil.

[Bunty]

It's been a complicated 5 months, starting with a very difficult operation to remove a brain tumour which required surgery as it was near the brain stem. Previously I have had about 5 brain mets successfully SRT. The operation was very successful in removing the tumour, however, it was a very difficult and long operation, and a lot of fluid had to be pumped into me. The fluid has resulted in me having to have a lot of draining of my tummy. Hospitalised for 7 weeks, with a lot of draining occurring, and since being home a few more. I looked and felt like I was 10 months pregnant. There is no free air in the abdomen or pelvis now.

My oncologist is not convinced the Enhertu is working for me, but of course we are still observing while I stay on Enhertu, which I have found to be quite an unusual chemo with strange reactions sometimes!

There is no active disease at the moment, but we have just started measuring the CEA. My CA 15.3 remains at a low level and no significant trend up.

Also there was another reason to consider going on to HER2Climb as there was noted a "smooth pleural thickening which may indicate overlying infection/inflammation".

I don't know how to answer your question, but I'll raise it with my oncologist. Many thanks.

Marie

[Bunty]

I had to have a very difficult brain tumour surgically removed about 5 months ago. Previously about 5 small tumours all slow growing have been treated successfully with SRT.

The operation was near the brain stem so could not risk SRT. It was a tough operation with a lot of fluid administered and that caused issues with much draining of tummy occurring. It seems to be controlled now.

A recent CT reported a "smoot

I'll stay on Enhertu at the moment, but there is a consideration now for the HER2 Climb. I don't know the answer to your question.

My CA15.3 is low and not trending upwards, but we have just started measuring CEA.

[Nguyen]

Below is the 5 Her2Climb trials. It’s unlikely you can get in 2 and 3 since you already had kadcyla (T-Dm1) and are having Enhertu. Enhertu should be helping you with your brain met. Tucatinib has some activities for brain met so a Her2climb trial is a good idea, or can you get it in Australia without going through a trial. If you are actually entering a trial, it is not likely that you can add another med to a trial beyond what are specified by the trial.

Regardless, Doxil is a “slow release less toxic” form of Adriamycin. You already had Adriamycin in the AC combination back in 2000. So you should remind your oncologist of this. Although I understand (can’t remember where I read it) after a long period of time (years) a previously used drug might work again.

If you can get genetic sequencing done on your tumor, discuss with your oncologist to sequence tissues from the all the met sites, particularly the brain and liver. Your tissue samples from previous operations should be stored in paraffin block somewhere. It’s likely tumor biology change with treatment (selection/survival pressure) and also from one met site (or primary) to the next.

Best wishes.


HER2CLIMB: Tucatinib plus capecitabine and trastuzumab versus capecitabine and trastuzumab alone 1.
HER2CLIMB-02: Tucatinib plus ado-trastuzumab emtansine (T-DM1) versus placebo plus T-DM1 2.
HER2CLIMB-03: Tucatinib plus trastuzumab deruxtecan (Enhertu) versus placebo plus Enhertu .
HER2CLIMB-04: Tucatinib plus trastuzumab and pertuzumab versus placebo plus trastuzumab and pertuzumab .
HER2CLIMB-05: Tucatinib plus trastuzumab and vinorelbine versus placebo plus trastuzumab and vinorelbine .

[Nguyen]

I now remember something that bother me a bit, in your 2014 biopsy you wrote now ER+ 90% staining, I assumed it’s still Her2 positive, based on continuing treatment with trastuzumab based therapy. Trastuzumab based therapy could negatively impact the heart, with LVEF of 4X percent, it is puzzling to consider adding doxil to any regiment with trastuzumab component. Doxil is in the anthracycline family and could impact the heart negatively in addition to trastuzumab based medicine. I hope your oncologist would closely monitor your heart perhaps monitoring GLS in addition to LVEF. GLS is a leading indicator of LVEF. If the oncologist is not familiar with GLS, perhaps consult a cardiologist for further opinion.

Lastly, one mechanism of resistance to regimens that target her2, is the tumor could change (or being more positive) to ER+ and/or PR+ from negative. I don’t see a component in the later regimens to block the ER/PR pathway. Since you had been treated with aromatase inhibitor before, your tumor likely develops ESR1 mutation. This can be checked with gene sequence, although I think there is a cheaper test. Aromatase Inhibitors do not work well (if at all) for tumor with ESR1 mutation. Fulvestrant/Faslodex will work to some degree. Perhaps you can also discuss all this with your oncologist.

Good luck.

[Nguyen]

Bunty or anyone else considering doxorubicin, go to the section articles of interest and take a look at the Gata-3 thread.