Recent approvals are driving a shift toward biomarker-informed treatment strategies, rational combinations and personalised sequencing.
For patients with advanced ovarian, cervical or endometrial cancer, the therapeutic landscape has historically been dominated by sequential chemotherapy, often associated with cumulative toxicity and modest response rates, particularly in later lines of treatment. The recent availability of multiple antibody–drug conjugates (ADCs) offers a new treatment paradigm in which tumour-associated antigen expression, payload sensitivity and toxicity profiles may increasingly inform more effective and rational therapeutic strategies.
The clearest example is mirvetuximab soravtansine (MIRV), a folate receptor alpha (FRα)-directed ADC delivering the maytansinoid microtubule inhibitor, DM4. MIRV initially received accelerated approval on the basis of SORAYA, a single-arm phase II trial in patients with FRα-high, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer who had previously received bevacizumab. In this difficult-to-treat population, MIRV produced clinically meaningful antitumour activity, with an objective response rate in approximately one-third of patients and durable responses in a subset. In 2024, the agent was approved by the U.S. Food and Drug Administration based on the results of the MIRASOL study, a randomised phase III trial comparing MIRV with investigator’s choice chemotherapy in patients with FRα-positive, platinum-resistant ovarian cancer. MIRASOL demonstrated significant improvements in progression-free survival, objective response rate and overall survival, establishing MIRV as the first biomarker-selected ADC to improve survival in platinum-resistant ovarian cancer. The practice-changing data came with new challenges for ovarian cancer clinics: the need for FRα testing and proactive management of treatment-related ocular toxicity.
Major advances in the field also came with tisotumab vedotin (TV) in recurrent or metastatic cervical cancer. TV targets tissue factor and delivers the microtubule-disrupting payload monomethyl auristatin E (MMAE). Its accelerated approval was based on innovaTV 204, a single-arm phase II trial in patients with recurrent or metastatic cervical cancer who had progressed after chemotherapy, in which TV showed reproducible activity in a population with limited treatment options. Full approval of TV was later granted on the basis of innovaTV 301, a global randomised phase III trial comparing TV with investigator’s choice chemotherapy in patients with previously treated recurrent or metastatic cervical cancer. Importantly, the study demonstrated an overall survival benefit, together with improvements in progression-free survival and objective response rate, moving this ADC from an active late-line option to a potentially practice-changing treatment. Similar to MIRV, clinical adoption of TV requires familiarity with toxicities that are not routinely encountered with conventional chemotherapy, including ocular events, bleeding and peripheral neuropathy.
Read full article: https://dailyreporter.esmo.org/esmo-gynaecological-cancers-congress-2026/editorial/the-antibody-drug-conjugate-era-in-gynaecological-cancers
