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Endometrial Cancer Q&A
Emerging Strategies for Better Endometrial Cancer Care: Answers to Frequently Asked Questions

Released: December 29, 2025

Nicoletta Colombo
Nicoletta Colombo, MD, PhD
Domenica Lorusso
Domenica Lorusso, MD, PhD, Prof
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Key Takeaways
  • Lenvatinib dose interruptions and dose reductions are an important clinical strategy to maintain patient adherence to pembrolizumab plus lenvatinib therapy.
  • Emerging antibody–drug conjugates targeting TROP2, FRα, and B7-H4 are showing promising activity in endometrial cancer.

During the recent live webinar, “Moving the Needle: Leveraging Emerging Strategies for Better Endometrial Cancer Care,” expert faculty discussed the latest data from major clinical studies and select trials with emerging therapeutics that are improving the care of patients with endometrial cancer (EC). In this commentary, Nicoletta Colombo, MD, PhD, and Domenica Lorusso, MD, PhD, Prof, answer audience questions that arose during the webinar, providing their perspectives on important issues related to the care of patients with EC.

Are there any data or case reports on the outcomes of patients who discontinue lenvatinib because of toxicity after starting treatment with pembrolizumab plus lenvatinib?

Nicoletta Colombo, MD, PhD:
Prospective data specifically on the outcomes of those patients who completely discontinue lenvatinib because of toxicity are lacking. However, before permanently discontinuing lenvatinib, healthcare professionals should consider dose interruptions and reductions, which were common in the KEYNOTE-775 trial. These results suggest that full-dose, continuous lenvatinib exposure is not required in all patients to maintain antitumor activity. From the starting dose of 20 mg/day orally, there are 3 lower dose levels (14 mg/day, 10 mg/day, and 8 mg/day) that can be attempted when patients are experiencing significant adverse events associated with lenvatinib, such as hypertension, diarrhea, fatigue, and others. This is important to keep in mind because lenvatinib toxicities are dose dependent and often reversible with dose modifications, and this may help patients remain on an effective regimen for a longer period of time.

Does the expression level of targets for antibody–drug conjugates correlate with activity? 

Domenica Lorusso, MD, PhD, Prof:
The relationship between antibody–drug conjugate (ADC) activity and target expression level in EC is unclear at this time and does not appear to be uniform across agents. For trastuzumab deruxtecan, higher target expression correlated with greater antitumor activity in the EC cohort of patients in the DESTINY-PanTumor02 trial (HER2 3+ overall response rate: 84.6%; HER2 2+ overall response rate: 47.1%). This high response rate may be related to HER2 being not only a target of the ADC but also being an oncogene. Trastuzumab deruxtecan is approved for patients with inoperable or metastatic solid tumors, including EC that express HER2 (IHC 3+), who have received prior systemic treatment and have no satisfactory alternatives. Other ADCs targeting TROP2, FRα, and B7-H4 generally seem to have response rates ranging from 20% to 40%, but these are very preliminary data from phase Ib trials. These trials enrolled patients regardless of target expression, although some may be stratifying based on this factor. Recent results reported at the International Gynecologic Cancer Society (IGCS) 2025 meeting for sacituzumab govitecan did not show a correlation between TROP2 expression and the efficacy of the drug. Several phase III studies of various ADCs in EC are currently ongoing and the related translational research projects will help answer this question.

What are your thoughts on the potential for ADC combinations or sequencing given the different targets?

Domenica Lorusso, MD, PhD, Prof:
At present, there are no ongoing trials formally testing ADC combinations or sequencing of ADCs. However, there is limited experience of prescribing an ADC for a patient following the use of another ADC that was linked to the same or a different payload. Such a scenario occurred in an ongoing phase I trial. The data suggested signals of retained efficacy, but the results are very preliminary.

Nicoletta Colombo, MD, PhD:
I agree. So far, there is no evidence of ADC combinations or an ideal sequence. Most ADCs have similar payloads, which weakens the rationale for combining them because of overlapping toxicity profiles. On the other hand, establishing the “right” sequence of ADCs, if one exists, might become a priority in the future. Ongoing phase III trials will generate additional data to eventually answer questions surrounding the sequencing of ADCs in patients with EC.

Your Thoughts
How do you select and sequence individualized treatment for patients with EC in your practice? What are your biggest challenges in the care of patients with EC?

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