Endometrial cancer is common, but once it spreads or returns after treatment, it becomes very difficult to manage. Clear treatment guidelines are limited, especially for aggressive subtypes like serous endometrial cancer, which grows quickly and often does not respond well to standard therapy. A new case report describes a rare and impressive response to trastuzumab deruxtecan (T-DXd), a targeted drug usually used for HER2-positive breast cancer. This patient’s cancer shrank completely after several prior therapies failed, offering hope for a group of women who historically have had few effective options.
This article explains what made this case unique, how the treatment worked, and why this breakthrough may influence future cancer care.
What Is HER2-Positive Serous Endometrial Cancer?
Endometrial cancer starts in the lining of the uterus. When it is caught early, most women do well. But serous endometrial cancer is different—it is rare, aggressive, and more likely to return or spread. Many tumors in this subtype have genetic changes, including:
- HER2 overexpression (found in about 35% of serous tumors)
- p53 mutations
- Mismatch repair deficiency (dMMR) in some rare cases
HER2 overexpression makes the cancer cells grow faster. In breast cancer, HER2-positive tumors can be treated with targeted drugs like trastuzumab or trastuzumab deruxtecan. But in endometrial cancer, HER2 is not routinely tested, and targeted HER2 treatments are not yet standard care.
The patient in this report had a uniquely challenging combination: serous endometrial cancer that was HER2-positive and also dMMR-positive, a combination rarely seen together.
What Is Trastuzumab Deruxtecan (T-DXd)?
Trastuzumab deruxtecan is an antibody–drug conjugate (ADC). It works in a two-part way:
- The antibody portion (trastuzumab) attaches to HER2 on cancer cells.
- The chemotherapy payload is then released directly into the tumor cell.
This design allows very potent chemotherapy to be delivered right where it’s needed, reducing damage to healthy cells. It also creates a “bystander effect,” meaning nearby cancer cells with lower HER2 levels can still be killed.
T-DXd has been successful in HER2-positive breast and gastric cancers, and growing evidence shows it may help other HER2-positive solid tumors as well.
How This Patient Was Treated Before T-DXd
The patient was a 72-year-old woman diagnosed with stage IIIA serous endometrial cancer. Over several years, she went through multiple treatments, including:
- Surgery
- Chemotherapy (carboplatin + paclitaxel) plus immunotherapy (avelumab)
- Pegylated liposomal doxorubicin (an anthracycline chemotherapy)
- Weekly paclitaxel after recurrence
Each therapy initially helped, but the cancer eventually returned or progressed. By early 2024, scans showed new tumor growth near the vaginal vault. Standard treatment options were nearly exhausted.
Her tumor showed strong HER2 staining (3+), so the medical team decided to start trastuzumab deruxtecan off-label.
What Happened After Starting T-DXd?
The patient began receiving T-DXd infusions every three weeks.
Exceptional Treatment Response
Immediately after starting T-DxD she also had a serious drop in white blood cells which led to a dose reduction. However, by December 2024—after four cycles—her PET/CT scan showed a complete metabolic response:
- The tumor at the vaginal vault disappeared
- Para-aortic and pelvic lymph node lesions resolved
- CA-125 blood levels returned to normal
She continued to feel better, with disease control lasting beyond eight months while still on therapy. Importantly, no heart or lung toxicity occurred during treatment, even with repeated monitoring.
Why This Case Matters
This is one of the clearest examples so far of deep and durable remission from T-DXd in metastatic HER2-positive endometrial cancer, especially after many other therapies failed. Key reasons this case is important include:
- Shows activity in a rare and difficult molecular subtype: HER2-positive + dMMR serous carcinoma
- Highlights T-DXd effectiveness even when HER2 expression was present in only about 20% of tumor cells
- Supports real-world evidence seen in early clinical trials like DESTINY-PanTumor-02
- Raises important questions about improving HER2 testing methods
- Suggests the need for phase 3 trials to confirm who benefits most
HER2-targeted therapy is not yet the standard for endometrial cancer, but cases like this demonstrate that some patients may benefit dramatically.
What This Could Mean for Future Treatment
As more evidence appears, HER2 testing may become a routine part of diagnosing serous endometrial cancer. This case also supports broader access to antibody–drug conjugates like T-DXd for patients with limited options.
Future progress may include:
- Better biomarkers to predict treatment response
- Trials combining HER2-targeted therapy with immunotherapy or other approaches
- Improved digital pathology to assess HER2 expression more accurately
For patients and clinicians, this case offers hope—and a reminder that personalized medicine is becoming increasingly important in gynecologic cancer care.
Source
Vida R, Bartoletti M, Lerda L, et al. Exceptional response to trastuzumab deruxtecan (T-DXd) in HER2-positive metastatic endometrial cancer. Curr Oncol. 2025;32:596.
Accessed by: https://pmc.ncbi.nlm.nih.gov/articles/PMC12651274/
