The introduction of ADCs into frontline ovarian cancer treatment creates a new challenge: conflicting biomarkers. A patient's tumor might be positive for both HER2 (an ADC target) and a BRCA mutation (a PARP inhibitor target), forcing clinicians to choose between two effective targeted therapies without clear guidance.

A "tsunami" of antibody-drug conjugates (ADCs) are in development for ovarian cancer, but many share the same TOP1 inhibitor payload. This creates a significant future clinical challenge: after a patient progresses on one such ADC, it is unknown if another with the same payload will be effective, creating an urgent need for sequencing data.

Real-world data shows that in platinum-sensitive ovarian cancer patients who have progressed on PARP inhibitors, subsequent platinum-based chemotherapy has a surprisingly low response rate of only 20%. This quantifies a significant opportunity for highly active ADCs to potentially replace platinum in this growing patient population.

Patients whose ovarian cancer progresses on the folate-targeted ADC mirvetuximab may still respond to a subsequent folate-targeted ADC with a different cytotoxic payload. This suggests that the folate receptor alpha target remains viable and that resistance may be payload-specific, opening new sequencing strategies.

A new wave of antibody-drug conjugates (ADCs) is transforming ovarian cancer treatment. These 'heat-seeking missiles' deliver potent chemotherapy payloads directly to tumor cells, achieving response rates from 23% to over 60% in biomarker-selected populations. This far surpasses the efficacy of conventional chemotherapy in resistant settings.

Retrospective data shows that using one Antibody-Drug Conjugate (ADC) after another, particularly those with the same class of payload like TOP1 inhibitors, results in a low response rate of 10-20%. This creates a significant unmet need and a major clinical challenge for patients who progress on a first-line ADC.

Most new antibody-drug conjugates (ADCs) for ovarian cancer use the same topoisomerase-1 (Topo1) inhibitor payload. This similarity will likely prevent their sequential use due to cross-resistance, forcing clinicians into a "one-shot" scenario where they must choose the single best Topo1-based ADC upfront for a patient.

As multiple effective Antibody-Drug Conjugates (ADCs) become available, the primary clinical challenge is no longer *if* they work, but *how* to use them best. Key unanswered questions involve optimal sequencing, dosing for treatment versus maintenance, and overall length of therapy, mirroring issues already seen in breast cancer.

Historically, therapies for platinum-resistant ovarian cancer were so ineffective that the order of administration was irrelevant. With the advent of multiple active ADCs, the concept of treatment sequencing and potential cross-resistance based on payloads or targets has become a critical, and entirely new, clinical consideration for this disease.