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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
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Antibody drug conjugates in gynaecological cancers: navigating between opportunities and challenges
Esteban Ciliberti1, Marta Nerone1, Vincenza Ricco1,2
1Medical Oncology, Oncology Institute of Southern Switzerland (IOSI), EOC, Bellinzona, Switzerland.
Abstract:
Antibody-drug conjugates (ADCs), which are tumor-targeting antibodies conjugated with cytotoxic chemotherapy agents, have emerged as a promising therapeutic approach in gynaecological cancers. Gynaecologicaal tumor-associated antigens targeted by ADCs include folate receptor-α (FRα), HER2, TROP2, tissue factor (TF), CDH6, CLDN6, B7-H4, B7-H3 and NaPi2b. Currently, three ADCs are clinically available for the treatment of gynaecological cancers: Mirvetuximab soravtansine for FRα-positive ovarian cancer, Tisotumab vedotin (targeting TF) for cervical cancer, and Trastuzumab deruxtecan for HER2-positive solid tumors. Various stages of investigation of ADCs as single agent or in combination treatments are ongoing with promising early signs of efficacy. Upon positive results from phase III trials, new treatment options will be available to reshape the standard of care of gynaecological malignancies and improve patients' outcome. This review summarizes the major clinical studies of ADCs in ovarian, endometrial and cervical cancer, and explores the main challenges related to their use in clinical practice.
Insights
Antibody-drug conjugates (ADCs) show promise for gynecological cancers. Ongoing trials and available treatments like Mirvetuximab soravtansine offer new hope for improving patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Gynecologic Oncology
Background:
- Antibody-drug conjugates (ADCs) represent a novel therapeutic strategy for gynecological cancers.
- ADCs combine targeted antibody delivery with potent cytotoxic chemotherapy agents.
- Several tumor-associated antigens are targeted by ADCs in gynecological malignancies.
Purpose of the Study:
- To review clinical studies of ADCs in ovarian, endometrial, and cervical cancers.
- To explore the efficacy and challenges of ADC utilization in gynecological malignancies.
- To summarize currently available and investigational ADCs for gynecological cancer treatment.
Main Methods:
- Review of major clinical studies involving ADCs in ovarian, endometrial, and cervical cancer.
- Analysis of data from ongoing phase III trials and early-phase investigations.
- Examination of challenges associated with clinical implementation of ADCs.
Main Results:
- Three ADCs are approved for gynecological cancers: Mirvetuximab soravtansine (FRα+ ovarian), Tisotumab vedotin (TF+ cervical), and Trastuzumab deruxtecan (HER2+ solid tumors).
- Numerous ADCs targeting antigens like FRα, HER2, TROP2, and TF are in various clinical investigation stages.
- Promising early efficacy signals are observed for ADCs as monotherapy and combination treatments.
Conclusions:
- ADCs are a rapidly advancing therapeutic frontier in gynecological oncology.
- Positive phase III trial outcomes are anticipated to significantly alter the standard of care.
- Addressing clinical challenges is crucial for maximizing the benefit of ADCs for patients.
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