New data presented at the recent Society for Gynecologic Oncology (SGO) 2026 Annual Meeting on Women’s Cancer highlighted how broader HER2 testing and emerging ADCs may expand treatment options in advanced and recurrent endometrial cancer. This article provides an overview of the clinical relevance of trastuzumab deruxtecan (T-DXd) and trastuzumab pamirtecan (T-Pam) as well as the evolving questions about efficacy, tolerability, and sequencing.

Following these presentations, featured expert Pamela T. Soliman, MD, MPH, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Clinical perspectives from Dr Soliman on these findings are presented here.

Based on early data in patients who express HER2, as part of standard of care in those with advanced uterine serous endometrial cancer, we often do HER2 testing at initial diagnosis because that affects our ability to give trastuzumab, which is commercially available for maintenance therapy in patients with advanced disease. Over the last couple of years, we have come to understand that it is good to test all patients with endometrial cancer—and gynecologic cancers in general—for HER2 because there are now US Food and Drug Administration (FDA)–approved drugs for patients who are high expressors in the recurrent setting.

T-DXd was rapidly approved by the FDA based on the biomarker-driven DESTINY-PanTumor02 trial, which included patients with different tumor types. In DESTINY-PanTumor02, for patients with endometrial cancer who had immunohistochemistry (IHC) 3+ staining for HER2, the overall response rate (ORR) was 84.6%. So, right now, you can give T-DXd to patients with HER2+ (IHC 3+) endometrial cancer as standard of care.

The final analysis of part 1 of DESTINY-PanTumor02 was presented at the SGO 2026 Annual Meeting on Women’s Cancer by Vicky Makker, MD. Even though there was a rapid FDA approval of T-DXd for HER2+ (IHC 3+) unresectable or metastatic solid tumors, including endometrial cancer, more information was needed. In this follow-up study, the confirmed ORR across all 267 patients with HER2-expressing IHC 3+ and 2+ disease was 37.5%, which was consistent with the initial analysis. So, this expanded data set helps confirm the promising results that were seen when the trial was first published.

We know that several modifications are being made to ADCs by different companies that hopefully will improve response rates or at least will improve the number of patients who may benefit from treatment. However, these modifications may also potentially impact side effects or toxicity. I think that a lot of these trials are now coming to fruition and there are still more data to present, and that is what we saw at the SGO meeting this year.

Another important presentation at the SGO 2026 Annual Meeting on Women’s Cancer was on a study of T-Pam by Bhavana Pothuri, MD, MS, and colleagues, which was selected as one of the main sessions because the study had a large cohort enrolled and an excellent response rate (abstract 03). T-Pam is a third-generation HER2-targeting ADC, so it is building on what we already knew but with modifications that hopefully will make it more effective in a higher percentage of patients with, potentially, a better side-effect profile. In this phase 1/2a trial, there was an endometrial cancer cohort of 145 patients with HER2-expressing advanced or metastatic disease who could be IHC 1+, 2+, or 3+ and who had received at least 1 prior line of therapy.

Not everyone had high HER2 expression: 40.7% were IHC 1+, 40.7% were IHC 2+, and 17.9% were IHC 3+ based on gastric scoring, which was also used in the DESTINY-PanTumor02 trial. All patients had prior chemotherapy, 75.9% had prior ICI therapy, and 21.4% had prior HER2-targeting therapy. This is important because, when you are looking at these novel drugs, you must understand whether they only work in someone who has not been exposed to HER2 treatments or whether there is also a cohort that could respond to a third-line or next-generation HER2-targeting drug.

The confirmed ORR was 44.1% across all HER2 expression levels, which is high, especially in a cohort in which not everyone had high HER2 expression. There were 55 patients who had a partial response and 8 patients who had a complete response. In this pretreated, advanced, recurrent population, it is remarkable to see complete responses to therapy. The median duration of response was 11.1 months across all HER2 expression levels. In HER2 IHC 1+ disease, there was a 34.5% confirmed ORR. The confirmed ORR was a little higher, 44.2%, in HER2 IHC 2+ disease and was 70.8% in HER2 IHC 3+ disease. As expected, the higher the expression, the higher the response rates, but, importantly, even in the IHC 1+ group, there were still patients who responded.

In the T-Pam study, grade 3 or higher treatment-related adverse events occurred in 46.9% of patients, which is similar to that reported for many ADCs. The most common (≥5%) were anemia, thrombocytopenia, and a decreased neutrophil count. Pneumonitis or interstitial lung disease, which can be harmful with some of these drugs, was relatively minimal at 4.1% of grade 3 or higher. So, overall, T-Pam has exciting potential for clinical benefit in women with endometrial cancer, even those with lower HER2 expression, and seemed to be well tolerated in this trial.

A key takeaway from these trials is that we should test everybody for HER2 expression. As more of these drugs come out, it may become less clear which drug should be used. We will have to determine which drugs have efficacy across broader numbers of patients, which drugs are most tolerable, and what the right timing is. Hopefully, ongoing trials will answer some of these questions for us.