Novel Agents in the Treatment of Patients With HER2-Positive Endometrial Cancer
In this video, Kari E. Hacker, MD, PhD, discusses the results of her team's study examining the rate of HER2-expression among patients with endometrial cancer, as well as the eligibility of these patient for novel therapeutics such as antibody drug conjugates. Dr Hacker presented this research at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting in San Diego, CA.
Additional Resource:
- Hacker KE, Allen K, Lee SS, Pothuri B. HER2 status among a cohort of endometrial cancer patients. Poster presented at: The Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA. Accessed March 22, 2024. www.sgo.org/events/annual-meeting/
For more SGO 2024 coverage, visit the Newsroom.
TRANSCRIPTION:
Kari Hacker, MD, PhD: I'm Kari Hacker, assistant professor at NYU Langone Perlmutter Cancer Center.
Consultant360: Could you give us a brief overview of your research and discuss why this objective was important to study?
KH: So we wanted to look at the proportion of newly diagnosed endometrial cancers that were HER2 positive, and we felt like this was an important question to answer based on the recent data that was presented from Destiny PanTumor 02.
And basically that data showed that HER2 positive endometrial cancers are sensitive or susceptible to treatment with trastuzumab deruxtecan, which is a HER2-directed antibody drug conjugate. And that study specifically looked at HER2 positivity based on IHC rather than HER2 amplification, which is what traditional HER2-directed therapies have targeted in endometrial cancer prior. And so again, based on that data and the potential for a new HER2 targeted therapy in endometrial cancer, we wanted to look at which specific endometrial cancers may be candidates for treatment with this new agent.
C360: It was noted in your research that new treatments have been approved for second-line treatment or are in development for HER-2 gynecologic cancers. Can you discuss the current standard of care for patients with HER2 endometrial cancer, and how these potential new treatments may shift clinical care for these patients?
Dr Hacker: The current treatment algorithm for HER2 positive cancers is specifically looking or targeted towards cancers that are amplified for HER2 and that amplification is determined by either a 3+ score on IHC or a FISH (fluorescence in situ hybridization) positive score if tumors are 2+ positive on HER2 IHC or for some other reason FISH was performed.
The study that looked at targeting HER2 in endometrial cancer specifically looked at one histologic subtype, which is the serous histologic subtype, and used trastuzumab, which is a monoclonal antibody against HER2.
There's currently one ongoing study looking at HER2-amplified endometrial cancers. And that specific study is defining HER2 positivity as again, HER2 amplification based on either 3+ IHC or 2+ IHC with FISH amplification. And then there was recently the Destiny PanTumor which was looking at the use of trastuzumab deruxtecan which is an antibody drug conjugate against HER2. And that study showed activity in HER2 2+ or 3+ IHC tumors, regardless of histology.
C360: Your study found that 60% of patients newly diagnosed with endometrial cancer in your study were HER2-expressing. Was this rate expected by your team, or were you surprised by this percentage?
Dr Hacker: So, as you mentioned, 60% of newly diagnosed endometrial cancers were HER2 expressing and that HER2 expression was determined by IHC, either 1+, 2+, or 3+. Approximately 30% were 2+ or 3+ positive on IHC, and I think we were surprised by those numbers. You know, in that context, almost 1/3 would be eligible for currently available HER2 ADCs or HER2 targeted therapies with the potential for up to 60% if 1+ on IHC shows a benefit with HER2 ADCs.
The one thing that I think we found most surprising was that there was HER2 positivity by IHC across all molecular subtypes and all histologies. There was a tendency to have higher levels of HER2 expression in the more aggressive molecular subtypes and histologic subtypes of endometrial cancer, which would include p53 aberrant molecular subclasses, or serous or carcinosarcoma histologies. But despite that tendency, we did see positivity across all molecular subtypes and all histologies, indicating that HER2 antibody drug conjugates may be potentially used in all endometrial cancers, not just specific molecular or histologic subclasses.
C360: What are the next steps for research in this area?
Dr Hacker: This was a single institution retrospective study, and thus it was fairly small with 147 patients included and only 124 of those patients had tumor testing for HER2 IHC. And so I think we would envision looking at a larger cohort of patients to confirm our data.
There are also ongoing studies looking at the use of HER2 antibody drug conjugates in HER2 expressing endometrial cancers, including not only the HER2 2+ and 3+ that were included in Destiny PanTumor but also endometrial cancers with lower HER2 expressing, including the HER2 1+ by IHC. So I think we're eagerly awaiting that data to get a good idea of how we can further target HER2 in endometrial cancer.
C360: Is there anything else that you would like to add today?
Dr Hacker: So in addition to seeing HER2 expression amongst all molecular subtypes and histologic subtypes, we also looked at HER2 expression based on stage at diagnosis. We did find that regardless of stage, we saw a high proportion of HER2 expression. However, there was much higher expression in patients that were diagnosed at later stage. So, by IHC 1+, 2+, or 3+, 90+ percentage of tumors were HER2 positive. And those tumors are much more likely to reccur and thus could potentially be targeted with HER2 antibody drug conjugates.
Well, thank you for having us and highlighting our study.