Real-World ADC Data Support Use in More Diverse Patients

Dr. Eliya Shachar, a postdoctoral research fellow in OB/GYN and urology at UCLA Health, discussed how real-world data may help address gaps in representation among patients receiving antibody-drug conjugates, or ADCs, in gynecologic cancers.

Shachar explained that ADCs have transformed treatment in advanced gynecologic cancers, improving survival outcomes in uterine, ovarian and cervical cancers. However, she noted that the pivotal trials leading to FDA approvals primarily enrolled patients who were White, younger, had good performance status and had received fewer prior lines of therapy.

Because of this, the study aimed to better reflect the patients seen in everyday clinical practice. Shachar said these patients are often more diverse, older and more heavily pretreated than those included in clinical trials. The goal was to determine whether this broader, more representative population benefits from ADCs in a way that is comparable to outcomes reported in clinical trials.

She also highlighted findings related to performance status, which measures a patient’s ability to carry out daily activities, such as whether they are out of bed or a chair for more than half the day. Shachar noted that performance status is often associated with prognosis.

In an initial univariate analysis, patients with poorer performance status had less optimal overall survival outcomes when treated with a specific ADC, norvituximab, in the platinum-resistant ovarian cancer setting. Similarly, in a cohort receiving trastuzumab deruxtecan (T-DXd), an ADC used for HER2-positive disease, performance status also appeared to be associated with survival outcomes.

However, when researchers conducted a multivariate analysis examining variables independently, performance status was no longer associated with survival outcomes. Shachar emphasized that these findings help provide a more nuanced understanding of how real-world patients respond to ADCs and may help guide treatment decisions for more diverse patient populations.

Cure: The background of your study notes that racial and ethnic minorities are often underrepresented in clinical trials. How does this real-world data help bridge the gap for patients from diverse backgrounds who might be hesitant about ADC treatments?

Dr. Shachar: So it’s true. Antibody-drug conjugates, or ADCs, are a new class of drugs that have really transformed the treatment landscape in advanced gynecologic cancer. They have improved survival in uterine, ovarian and cervical cancers. However, the pivotal trials that led to their FDA approvals largely included patients who were predominantly White, younger, had good performance status and had received fewer prior lines of therapy.

Our key question was to better understand whether the patients we see in clinic, who are often more diverse, older and more heavily pretreated, benefit in the same way as those included in the trials. That is exactly what we wanted to study — whether this more representative, real-world patient population benefits equally and comparably to what was seen in the trials that led to these drug approvals.

Transcript has been edited for clarity and conciseness.

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