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Dr. Campos:
This is CME on ReachMD, and I'm Dr. Susanna Campos.
Dr. Salani:
And I'm Dr. Ritu Salani.
Dr. Campos:
I'd like to discuss a case with you. It's a very interesting case that I saw at my clinic. This is a 45-year-old woman who was diagnosed with a stage IIIC high-grade serous carcinoma of the fallopian tube. She was optimally debulked, and her tumor was found to be BRCA negative and HRD negative. She underwent adjuvant chemotherapy with carboplatin and paclitaxel plus bevacizumab, followed by bevacizumab maintenance. Unfortunately, she recurred less than 6 months after the completion of chemotherapy, namely the carboplatin and the paclitaxel. The patient’s CA125 started to climb, and imaging studies revealed marked retroperitoneal adenopathy.
We tested her for the folate receptor alpha, which was negative. But when we tested her for HER2/neu IHC, it was 2+. The patient went on to be treated with trastuzumab DXd and had a partial response to therapy. She continues on trastuzumab DXd at this current time, and she's also not having any significant pulmonary side effects.
Dr. Salani:
Yeah, that's a great case. And I think this is also a really exciting area of development that we're starting to explore in gynecologic malignancies. And just to highlight, there was a study, a basket trial, looking at the role of trastuzumab deruxtecan in different tumor types, and the goal was to look at patients who had IHC 2+ or 3+ expression. And they used a gastric-type testing, and typically, we’d been using breast cancer IHC testing, historically. And the study showed just really pronounced responses across the board. And I'll focus on the gynecological malignancies, and in this case, ovarian cancer.
What was really interesting is that the patients who had 3+ expression had the most pronounced response, but 2+ also had a notable response. And many of the ovarian cancer patients were heavily pretreated patients where we often don't have any strategies that have really significant impact and efficacy but really do have significant toxicities. And so having HER2 expression, I think, is really something that we're all looking for and hoping to find in many of our patients, because we now have a very effective strategy for many of these patients. And I love this case because I think it highlights the youth of this patient, the ability to tolerate a therapy that has a targeted approach, and that it's able to be managed with limited toxicities, although we cannot understate the importance of monitoring those. And you’d mentioned the pulmonary toxicities, which we really do need to stay on top of, both with imaging and with symptom review.
Dr. Campos:
I completely agree. And I think we all struggle with platinum-resistant ovarian cancer. The regimens prior to some of these ADCs were just not as robust as these patients needed. And I think that, as you described, the DESTINY-PanTumor02 trial really opened the door to another treatment regimen for these individuals. And I don't think we've seen gynecological surgical oncologists and medical oncologists so excited in a long time, because now we have this particular drug that has very robust activity in ovarian cancer. In the guidelines, as we all know, the FDA approved trastuzumab DXd for HER2/neu IHC 3+. But based on the data for the DESTINY-PanTumor trial that’s now published in JCO, the NCCN panel felt as though it was appropriate for both IHC 2+ as well as 3+, really expanding the patient population that we reach.
Dr. Salani:
And I think, just to capitalize on it, you mentioned that she was tested for alpha folate receptor as well, and I just want to highlight that that's another treatment option or strategy that we have for patients with platinum-resistant ovarian cancer. We use 75% expression, and although there are studies and different drugs looking at different expression rates, and that's another option that's both FDA-approved and in the NCCN Guidelines for those patients who have that expression. So I think it's another important opportunity.
This patient was negative, so not an option for her, but I think this highlights the role of biomarker exploration in these patients, especially where there are limited treatments.
Dr. Campos:
And I think that we can't say enough. There's so many antibody-drug conjugates that are coming our way and the importance of clinical trials, and this is exactly how we have this drug at our disposal at this time.
Dr. Salani:
A very exciting area.
Dr. Campos:
Absolutely. Well with that, our time is up. We hope you found this case quite helpful. Thank you so very much for listening.
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