Advances in antibody-drug conjugates for gynecologic malignancies

Antibody-drug conjugates (ADCs) represent a new class of drugs that combine a surface receptor-targeting antibody linked to a cytotoxic molecule delivering the potent cytotoxic payload directly to tumor cells. This review summarizes the current literature demonstrating their use in the treatment of gynecologic malignancies.

Tisotumab vedotin is the first U.S. Food and Drug Administration (FDA) approved ADC for the treatment of gynecologic cancers. While in the phase 3 randomized controlled trial in platinum resistant ovarian cancer patients, FORWARD 1, mirvetuximab did not meet its primary endpoint of progression-free survival. But we await more recent data from the two ongoing phase 3 trials of mirvetuximab in recurrent ovarian cancer patients. HER2/neu, Napi2b, mesothelin, and human trophoblast cell-surface marker (Trop-2) overexpression have also been exploited as excellent targets by novel ADCs in multiple tumors including ovarian, endometrial, and cervical cancers.

Current evidence strongly supports the use of ADCs and ongoing clinical trials will provide further information into the potential of making these drugs part of current standard practice allowing patients to be treated with a higher level of personalized cancer care.