Trastuzumab Deruxtecan: Effects in Multiple Cancer Types

Dr Maurie Markman discusses the concept of focusing on a particular molecular target and then potentially looking at the value of that drug across multiple tumor types.
www.medscape.com/viewarticle/...
-- TRANSCRIPT --
Hello. I'm Dr Maurie Markman, from City of Hope. I'm delighted to briefly discuss with you a fascinating paper that just appeared in the Journal of Clinical Oncology, and there's actually been a large amount of discussion about it since the original abstract came out several months before. The paper is entitled "Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the Destiny-PanTumor02 Phase II Trial."
This is a fascinating study. Antibody-drug conjugates, of course, have had a large amount of interest and work going on now for a number of years. The concept of focusing on a particular molecular target and then potentially looking at the value of that drug across multiple tumor types, assuming the target is present, has really been a palpable discussion within the oncology community, and this particular research study addresses this.
This drug that I noted has already been FDA approved in HER2-expressing breast and gastric cancers, as well as HER2-mutant non-small cell lung cancer. The specific study here was looking at other tumor types, not the ones that are already approved, and tumors that had immunohistochemical staining, or IHC, of 3+ or 2+ by local labs were eligible for the trial.
A number of tumor types were looked at in this trial, including endometrial, ovarian, cervical, bladder, biliary tract, pancreatic, and others. I'm going to focus, in a moment, on the gynecologic cancers, which is my own clinical and research interest.
The bottom line is that, in this population of patients who had at least one prior therapy before the trial, or in settings where there was no standard-of-care option, the objective response rate overall was 37.5%. In those individuals who were 3+, the objective response rate was considerably higher than that.
As I noted, if you look at the data specifically in endometrial cancers, cervical cancer, and ovarian cancer, again, 2+ or 3+ staining, the endometrial cancer objective response rate was 57.5%, cervical cancer was 37.5%, and ovarian cancer was 42.5%. When you then look specifically at the 3+ staining, the actual objective response rates - remembering that the numbers get small - were even considerably higher.
I should also note that even though the eligibility for this trial was at least one prior regimen, in the case of endometrial, cervical, and ovarian cancer, the patients on the trial actually received, depending on the tumor type, at least two and sometimes up to three, four, or more regimens.
This is fascinating. Here, we have a situation where there is evidence of overexpression of HER2 in the three gynecologic malignancies - that is, three different tumor types. We have objective response rates of over 40%, and those responses lasted a very reasonable period of time.
Very soon, I think we can say that we will have a new therapeutic option for these tumor types in patients who have failed to respond to initial or standard therapies to date. Very importantly, we're talking here now about increasingly molecular-based therapies, although there is a small percentage of patients in each of the tumor types, but where that target is present, this is a very reasonable therapeutic option available for these patients.
I would encourage all oncologists, patients with these malignancies, and their families to see this paper or the highlights of this paper. There will be more information coming out about this drug in their future, as well as antibody-drug conjugates in general and molecular targeted therapy and precision medicine in oncology, which, of course, is the critical future of drug development in this area. I thank you for your attention.
Transcript in its entirety can be found by clicking here: www.medscape.com/viewarticle/...