Antibody-drug conjugates (ADCs) are expanding treatment options for patients with gynecologic cancers. ADCs are administered intravenously and combine an antibody with a chemotherapy agent. The antibody acts as a delivery mechanism, releasing the payload directly into the tumor and neighboring cells.

Duke experts are at the forefront of these targeted therapies, which are showing particular promise in recurrent ovarian, endometrial, and cervical cancers. One ADC, trastuzumab deruxtecan (T-DXd), is generating excitement with response rates of up to 80% in patients with unresectable or metastatic HER2-expressing gynecologic cancers.

"FDA approved T-DXd (fam-trastuzumab deruxtecan-nxki) for patients with HER2 3+ expressing solid tumors, regardless of where the cancer first started growing. This was a tumor-agnostic approval which is really amazing. T-DXd is a very interesting drug. It combines a HER2-targeting monoclonal antibody with a chemotherapy topoisomerase 1 inhibitor payload (DXd) and has shown very positive results in landmark trials such as DESTINY-PanTumor02," says gynecologic oncologist Angeles Alvarez Secord, MD, MHSc. "This treatment shows that we can effectively target cancer cells with precision."

The National Comprehensive Cancer Network guidelines expanded the use of T-DXd for patients with select HER2 2+-expressing gynecologic cancers.

Biomarker testing is becoming increasingly important at diagnosis and recurrence. Molecular markers can directly influence eligibility for T-DXd and other ADC therapies, as well as emerging clinical trials.

"To qualify for T-DXd, patients must have a HER2 biomarker immunohistochemistry score of 2+ or 3+," says Secord.

At Duke, Secord notes that studies supporting T-DXd were based on gastric HER2 scoring. "This differs from breast and endometrial scoring. We're now working with our Duke pathologists to use gastric scoring for appropriate patients to help guide treatment decisions and improve outcomes," she says.

Secord is also actively involved in studies examining tumor tissue and blood samples collected before, during, and after treatment to identify biomarkers that may help predict which patients will, or will not, benefit from T-DXd and other ADCs.

Referring providers should also be aware that ADCs have unique toxicity profiles, including interstitial lung disease/pneumonitis associated with T-DXd.

"It's important that these treatments be administered by experienced centers with specialists who know how to prevent, recognize, and manage these toxicities," says Secord.

For this reason, referring patients to a center with expertise in treating patients receiving ADCs is critical. ADCs are helping move gynecologic oncology toward more targeted, effective, and individualized care. Early referral for patients with recurrent or chemotherapy-resistant disease can provide access to new treatment options beyond traditional chemotherapy and immunotherapy.

"We are monitoring ongoing ADC trials and are eager to offer the latest evidence-based therapies to our patients," says Secord.

Secord serves as the global principal investigator for the phase 3 RAINFOL-02 trial evaluating rinatabart sesutecan (Rina-S) trial, which is studying an ADC designed to target folate receptor alpha (FRα) in platinum-resistant ovarian cancer and the site PI for the ongoing phase 3 RAINFOL-03 trial evaluating Rina-S in patients with recurrent endometrial cancer.