The simultaneous or sequential presentation of cervical and breast cancer is rare, especially under systemic treatment. The patient's cervical cancer was aggressive, and the subsequent metachronous breast cancer highlights the complex, multifactorial nature of carcinogenesis. The development of a second primary malignancy while a patient is receiving treatment for a metastatic condition is a critical clinical scenario, necessitating individualized treatment strategies, as optimal management remains unclear due to the rarity of such cases.

Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens-neoadjuvant chemotherapy and adjuvant CPI therapy-have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer.

P1, N=200, Recruiting, Sutro Biopharma, Inc.

P2, N=352, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Sep 2025 --> Jan 2026

For cervical, vulvar and vaginal cancers specifically, trastuzumab deruxtecan and tisotumab vedotin could be important therapeutic options in the right context. In this review, we describe the molecular features of different cervical, vulvar and vaginal cancer types, current genomically-matched therapies being investigated and discuss treatment strategies with future potential.

Agents such as mirvetuximab soravtansine, and tisotumab vedotin, targeting folate receptor alpha and tissue factor, respectively, reported clinical efficacy in patients with limited options. Comprehensive management of ocular toxicities is essential to ensure the safe and sustained use of ADCs, preserving both therapeutic benefit and patient well-being. Further research is warranted to optimize preventive and management protocols.

Ocular adverse events (AEs) are common among ADCs with tubulin-targeted active agents, such as belantamab mafodotin, tisotumab vedotin and mirvetuximab soravtansine (MIRV). Support from ophthalmologists is essential to AE management to allow MIRV therapy to continue. This review provides ophthalmologists with a clinical overview of ocular AEs associated with certain tubulin-acting ADCs, with a focus on MIRV, and the prophylactic/mitigative measures that can allow patients to stay on MIRV therapy longer.

P3, N=231, Not yet recruiting, Shanghai Miracogen Inc.

P1, N=150, Recruiting, Exelixis

P1, N=210, Recruiting, Adcendo ApS | N=66 --> 210

With the approval of tisotumab vedotin (TV), a tissue factor (TF)-targeting ADC, for the treatment of r/mCC, an increasing number of ADCs targeting different antigens have demonstrated highly encouraging therapeutic potential in cervical cancer patients...This review outlines promising tumor-associated antigens (TAAs) for ADC targeting in cervical cancer and their biological functions, such as human epidermal growth factor receptor 2 (HER2), trophoblast cell surface antigen 2 (Trop-2), mesothelin, nectin cell adhesion molecule 4 (Nectin-4). We also summarize the clinical applications and research progress of corresponding ADC, and provide novel perspectives for future ADC development and clinical research strategies.

P4, N=100, Recruiting, Pfizer | Not yet recruiting --> Recruiting