The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–)breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.
Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it's still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.
"Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us," he said.
"First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC Enhertu (trastuzumab deruxtecan). Would I rather give Dato over one of these? I don't have an answer," he added.
In addition, it's unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.
"I would say that the elephant in the room is really another question, and that is, 'Is Dato-DXd in this context delivering on the promise of an ADC?' " Dr. Chandarlapaty said.
"I think translational research is urgently needed if we're ultimately to deliver on the promise of these agents in the clinic," he concluded.
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Kerryd22
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Thanks for sharing Kerry. I was reading several professional articles on this last week. I think the ADC's in general are very promising but there are still so many unknowns with this particular one that I personally don't get excited yet. As with all the ADC's they are geared towards patients that have already received one or two previous chemotherapy regimes. What I wish would happen with these new promising drugs is that they could be trialed for effectiveness with patients that have progressed past endocrine therapies and had not yet taken infusion chemotherapy. If as they promote it carries less side effects then this would be the ideal area for it to be trialed in my opinion. Keep in mind that the ADC'S also are always given along with a chemotherapy agent too so really we are starting to look at the sub-group of heavily pretreated to qualify. So perhaps good news...but needs much more research I think.
Actually, Enhertu, an ADC, is given alone. It does have potentially a lot of side effects — the usual assortment—but is apparently very effective and now used for Er+.
Yes thank you for clarifying. It is used for ER+ but also the patient has to be HER2 low as I understand. I also must say that I am Canadian and as such often look at things through that lens. Where I receive my treatments it is still only approved for patients with HER2+ and HER2 low is not yet recognized. Take care.
Yes, it is definitely given to her2 low. I recently had the Guardant360 blood test that showed that I developed a mutation in the her2 gene (not her2 positive though) which can also be treated by Enhertu… not sure if it has been approved by fda but my onco is excited about that. He said that he gives Enhertu for her2 mutations in lung cancer.
Yes for some reason drugs that test favorably in clinical trials for solid tumors of the lung seem to also do well in breast cancer. Another thing to note is ADC's in general have been around since I believe 2000 was the first one approved by FDA for AML. However the first approved one for breast cancer was not approved until 2013 which was Trastuzumab emtansine (Kadcyla). Since then the work has been mostly focused on TNBC and HER2+ so it is exciting to see the research now branching out to include in reality the most common type. Let's all hope that it continues to be a focus of research and clinical trials.
There is a miraculous one in clinical trials for a formerly quickly terminal brain cancer (glioblastoma). There was a documentary on PBS that explained how that ADC works. The researcher who developed it used a disabled polio virus that could penetrate the cancer cells, which have a protective barrier, and deliver the chemo. Saved lives, until they decided to double the payload, and killed people with their immune response.
I think both of us probably face the same restrictions within our cancer drug choices. However that just means that we have to keep thriving with each line of treatment as long as virtually possible and perhaps then the caveats for accessibility will be removed. That's my plan anyway. Take care.
Thanks for clarifying, Awesome. You seem to have a good understanding of the medical research. Do you have some training?
I must have attended the same webinar as Best521. The ADCs (anti-body drug conjugates) are just a delivery system that helps a chemotherapy penetrate the cancer cell. They have been found to greatly increase the effectiveness of the chemo. Enhertu is both an ADC and chemo. The good news is that it can spread the bioavailability to adjacent cancer cells. It was twice as effective as chemo delivered systemically, without the ADC. The bad news is that the side effects are the same as the chemo delivered generally, systemically, not targeted. They seem to attach to healthy cells as well.
There are many ADCs coming to market or going into trial, for different varieties of mbc (triple negative, HER2 low, ER+ were mentioned).
I agree it's exciting that new treatment options are on the horizon and as the patents get closer to expiring on some of the CDK 4/6 inhibitors you can bet those drug companies are working hard to have the newest and greatest...which of course works to our benefit. I do have a long medical background and a keen interest in research. Thanks for asking.
The patents are expiring? There will be generics? I had to get Ibrance and Verzenio free through the pharmaceuticals' patient assistance program. There is a woman on the board from England who wants to try a second CDK4/6 but it isn't supported in England and she was thinking of paying out of pocket.
I am now going on ribociclib and will have to find a way to get it free -- but if it is going generic, I won't have to.
What is your long medical background? (I am an experimental psychologist, so know how to read research findings generally, research design and stat testing, but get lost in the chemical language.)
Ribociclib patent expires in 2031. They don't expect a generic to be available until 2034. Too far away for me! Nothing has worked for more than two years. Eight years would be fantastic, but not realistic.
I should clarify that yes most of us with our everchanging disease cannot rely on the generics of these drugs.....Ibrance primary patent got extended to expire in 2027, Ribociclib primary patents expire in 2027-2029 and Abemaciclib primary patents expire in 2029. Although a long time away in our minds, pharmaceuticals need some much R & D that is no time at all for them.
I understand the situation of the lady from England. It's the same here in Canada. If you have received one CDK 4/6 inhibitor you will not be funded for another one. That's typical in a government funded healthcare system.
It sounds as if we did attend the same seminar. A couple of things to note Trodelvy delivers a payload of chemotherapy, (Irrinotecan) four times greater than traditional systemic chemotherapy, a level which would otherwise be far too toxic. My care team assures me Trodelvy side effects are not as intense as traditional chemotherapy, although there is some leakage which will cause side effects. Based on annectodal conversations with others I confirmed the same.
The results so far have been amazing, looking forward to my next scan in a couple of weeks to see where things are 🤞
Yes I am on Trodelvy and as excited about the promise of ADCs as are the top Cancer Research Scientists and Oncologists. I even skipped over Xeloda to try Trodelvy. My oncologist assured me Xeloda will always be there. We will also look into other oral treatments in the future. My hair is gone, however after 16 months on Ibrance it was absolutely awful looking, my eyelashes and eyebrows were already gone. I was ready to let go of the straggles of hair that remained for the promise of an effective treatment. The day will come when my hair grows back. Still haven’t purchased a wig yet, but very comfortable without one. Have some cute hats. My morning routine takes much less time without the hair. ☺️ It’s all about buying yourself more time until the next best treatment comes along.
Yes it is good news! I just attended a seminar where they called this time in MBC treatment the ADC Era. ADCs are controlling MBC three times longer than traditional systemic chemotherapy with less side effects, although side effects remain. I am on the ADC Trodelvy or Sacituzamab Govitecan. This is my first chemotherapy. I have never had chemotherapy before and did not have chemotherapy when my cancer first occurred in 2017, only radiation. With Trodelvy my first scan showed substantial decrease in the size of the tumors, more than I had with Ibrance and Letrozole. Currently there are many more ADCs in the pipeline, many targeting different antigens/proteins on the cell surface. There are trials available for new ADCs in the pipeline.
The new ADCs provide hope. There are more options, more tools in the toolbox, more opportunities for a longer life 🥰
A short video presentation (less than 2 minutes) on the take away from the TROPION-Breast01 phase 3 trial and optimism from a breast oncologist from Dana Farber.
That presentation skims over the fact that what the ADC Data DXD delivers is Enhertu (TRASTUZUMAB DERUXTECAN). She contrasts DataDXD with chemo, but Enhertu is chemo. The trial was used specifically used for HER2+. (Also, as others have complained here, one has to have had 1 or 2 lines of chemo to qualify.)
So it is good news for those who have had previous chemo and who are HER2+ and for whom Enhertu is appropriate.
Totally agree with you. I was one of the posters that complained about having to basically be heavily pre-treated with previous chemotherapies to qualify. However I posted because I know many people probably fit those criteria.
I thought her presentation was disingenuous in contrasting the ADC with chemo, when what it delivers IS chemo. In the EMBRACE webinar on ADCs on Saturday, they said that mostly, despite the targeted delivery, patients experience the full range of chemo side effects from whatever drug is delivered, speculating that there was some leakage.
What is unique about this ADC, according to the link you posted, is that the side effects were diminished. That is big news. Better delivery and effectiveness, and reduction of side effects. I just wish the emphasis had been different and more accurate: This is a better way to take Enhertu for HER2+.
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