Efficacy, Tolerability, and Quality of Life with ADCs in Gynecological Malignancies

EP: 1.Molecular Testing in Ovarian and Endometrial Cancer: Evolving Approaches and Best Practices

EP: 2.Expert Perspectives: Standardizing HER2 Testing in Gynecological Cancer

EP: 3.Integrating T-DXd in HER2+  Gynecologic Cancers: Impact on Treatment Decisions and Sequencing

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EP: 4.Efficacy, Tolerability, and Quality of Life with ADCs in Gynecological Malignancies

EP: 5.Navigating Treatment Sequencing Decisions in the Ovarian Cancer Paradigm

EP: 6.Exploring Emerging ADCs and Their Potential Impact in Gynecologic Cancers

The recent accelerated approval of T-DXd has brought a promising new option to patients with limited access to clinical trials, especially those with HER2-positive gynecologic cancers. Both clinicians reflect positively on the broader availability of this drug, noting that it offers a viable alternative where few effective treatments previously existed. While acknowledging the importance of this regulatory milestone, they also emphasize the need for confirmatory trials to better define patient selection, optimal testing methodologies, and treatment sequencing strategies.

In clinical practice, their experiences with T-DXd have been mixed. While some patients, particularly those with HER2/3+ expression, have experienced significant and prolonged responses—such as a 9-month benefit in a platinum-resistant ovarian cancer case—others have shown early disease progression. This variation in response has tempered initial enthusiasm and highlighted the need for improved biomarkers or testing strategies beyond immunohistochemistry alone. The clinicians also express caution in patient counseling, aiming to balance hope with realism based on emerging real-world data.

Regarding tolerability, T-DXd and other deruxtecan-based antibody-drug conjugates (ADCs) have generally been well received by patients. The absence of common chemotherapy-related toxicities such as alopecia and neuropathy has allowed many patients to maintain a higher quality of life, even during extended treatment periods. However, the risk of pneumonitis remains a concern, especially in those with prior exposure to other agents with pulmonary toxicity. Compared with other ADC payloads such as MMAEs and exatecans—which may be more hematologically toxic—the deruxtecan platform appears more manageable when appropriate antiemetic prophylaxis is in place. As new ADCs are developed, clinicians anticipate further refinement in selecting therapies based on target specificity and toxicity profiles, with the hope of achieving deeper, longer-lasting responses and potentially earlier integration into treatment algorithms.