Introduction

Gynecologic cancers, specifically ovarian, uterine, and cervical cancers, remain a significant health burden in females. Over 106,340 new gynecologic cancer cases and 32,280 deaths are estimated in the USA in 2023 [1]. Estimated 5-year survival rates for patients with metastatic disease are 20–40% for ovarian cancer, 10–15% for uterine cancer, and 16–30% for cervical cancer [2,3,4]. First-line treatment for advanced-stage gynecologic malignancies typically includes systemic therapy and surgery for ovarian cancer, systemic therapy with or without radiation therapy and surgery for uterine cancer and systemic therapy with or without radiation for cervical cancer [5,6,7].

Biomarker-directed targeted therapies have increasingly become an area of focus for management of gynecologic cancers. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, improved progression-free survival (PFS) for patients with ovarian cancer in various settings including frontline, frontline maintenance, platinum-sensitive recurrence, and platinum-resistant recurrence [8,9,10]. Patients with advanced-stage cervical cancer experienced overall survival (OS) benefits with bevacizumab in combination with platinum doublet chemotherapy for primary treatment [11]. In ovarian cancer, poly (ADP-ribose) polymerase (PARP) inhibitor maintenance therapy demonstrated PFS benefit in those with germline BRCA mutations or homologous recombination deficiency [12,13,14]. Pembrolizumab and dostarlimab, immune checkpoint inhibitors against programmed cell death protein 1 (PD-1), are approved in several settings for patients with gynecologic malignancies. Pembrolizumab monotherapy demonstrated improved PFS in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) endometrial cancer with progression on prior treatment [15,16,17]. Pembrolizumab with standard chemotherapy for advanced or recurrent endometrial cancer significantly prolonged PFS compared to chemotherapy alone [18]. Dostarlimab with carboplatin and paclitaxel significantly improved PFS in patients with advanced or recurrent endometrial cancer, and patients with dMMR and MSI-H tumors had substantial benefit [19]. Lastly, pembrolizumab demonstrated PFS and OS benefits for patients with programmed death ligand 1 (PD-L1)-positive persistent, recurrent, or metastatic cervical cancer when given in combination with chemotherapy with or without bevacizumab [20].

Despite these treatment options and advances, advanced or recurrent gynecologic cancers are still often incurable, and patients frequently exhaust several therapeutic options. Chemotherapy can also significantly impact patient quality of life due to a range of toxicities [21]. Given the poor prognoses, low response rates, toxicities, and risk of chemotherapy resistance with metastatic or recurrent disease, additional strategies are needed to develop well-tolerated and effective treatment options. Antibody-drug conjugates (ADCs) are a novel class of targeted therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using interactions between antigens and antibodies [22]. The purpose of this review is to explain the structure and mechanism of action of ADCs, summarize the current state of ADCs approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

Antibody-drug conjugate structure and mechanism of action

ADCs are composed of a monoclonal antibody, a cytotoxic payload, and a linker which joins the antibody and payload. Each element contributes to the clinical effects of the ADC. The general mechanism by which ADCs act on tumor cells occurs through a series of events (Fig. 1): (1) antibody binds to a target antigen on tumor cell, (2) antibody-drug complex is internalized through receptor-mediated endocytosis, (3) complex is degraded through endolysosomal processing, (4) payload is released into the cytoplasm, and (5) cell death due to DNA damage or microtubule disruption [23, 24].

Fig. 1
figure 1

The mechanism of action of antibody-drug conjugates.

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Antibody

The antibody binds to a specific target antigen which should be hyper-expressed on the surface of tumor cells compared to normal cells, thus increasing the chance of the ADC binding to a tumor cell [25]. Ideally, the target antigen should be expressed extracellularly to be recognized by the ADC and internalized to transport the ADC into the cell [26]. IgG is the most common immunoglobulin used for ADCs due to high binding affinity with the Fc portion of IgG1 and efficacy with antibody-dependent cell-mediated cytotoxicity. A humanized or chimeric immunoglobulin backbone is typically used in ADCs to decrease immunogenicity [24]. Other modifications can be made to immunoglobulins to improve payload stability, reduce toxicity, or enhance anti-tumor effects [27,28,29]. Intratumor heterogeneity, in which some tumor cells do not express the target antigen, may present challenges with ADCs [30].

Payload

The second component of an ADC is the payload, a highly potent, cytotoxic molecule which induces cell death [31, 32]. The most used payloads are agents that cause DNA damage or disrupt microtubules. For example, auristatins (monomethyl auristatin E [MMAE] and monomethyl auristatin F [MMAF]) and maytansinoids (DM1 and DM4) are common payload classes which act as microtubule inhibitors, target proliferating cells, and cause cell cycle arrest. DNA-damaging payload classes include the calicheamicins including ozogamicin, which bind the minor groove of DNA to cause double strand breaks, and camptothecin analogues including SN-38 and DXd, which inhibit topoisomerase I. DNA-damaging payloads are more potent than antimicrotubule agents and capable of non-cell cycle specific cytotoxicity, which may make them more effective in tumors with lower mitotic rates [24, 33]. The drug-to-antibody ratio (DAR) refers to the average number of payload molecules conjugated to the antibody, and a higher DAR typically reflects higher potency [34].

Linker

The linker component of the ADC binds the payload to the monoclonal antibody to facilitate payload delivery to the target cell [35]. Thus, the linker must be stable in plasma to avoid deconjugation prior to delivery to the tumor cell, as premature release can lead to systemic, off-target toxicity [24]. There are two general classes of linkers: cleavable and non-cleavable. Cleavable linkers, including disulfide linkers and dipeptide linkers, are cleaved based on sensitivity to the intracellular environment, including the pH, glutathione levels, or sensitivity to intracellular enzymatic proteolysis [36]. This leads to preferential release of the payload within tumor cells. However, the plasma stability of cleavable linkers varies and may allow for extracellular payload release. Additionally, hydrophobic payloads can diffuse through the tumor cell membrane after being cleaved from the ADC intracellularly. Extracellular delivery of the payload through these mechanisms leads to the bystander effect. The bystander effect refers to the cytotoxic effect of the payload on nearby tumor cells without expression of the target antigen, which can be advantageous if the tumor has heterogenous expression of the selected antigen [37]. However, the bystander effect can distribute the payload to normal tissues and exacerbate ADC toxicities [38]. Non-cleavable linkers such as succinimidyl 4-N-maleimidomethyl cyclohexane-1-carboxylate release the payload intracellularly upon lysosomal degradation of the monoclonal antibody rather than the linker. Through this process, the payload often retains charged amino acids, which limits membrane permeability and prevents extracellular diffusion. Non-cleavable linkers offer the advantage of enhanced plasma stability, leading to a broader therapeutic index. However, they do not allow for bystander killing, which may limit activity in certain settings [39].

Toxicity profile of antibody drug conjugates

Despite the ability of ADCs to target tumor cells and limit exposure to healthy tissues, toxicities from ADCs remain prevalent. Toxicity of an ADC is determined primarily by the payload function but can also be influenced by the nature of the linker, presence of the target antigen on non-malignant cells, the bystander effect, and cancer type. A recent meta-analysis on ADCs found that hematologic, neurologic, ophthalmic, and hepatic toxicities are consistently reported [40]. Grade 3 or higher hematologic toxicities have been noted with several payload classes and types including the auristatins (particularly MMAE), calicheamicins, maytansinoids, and SN-38 [26, 41]. Ocular toxicity is prevalent with use of tisotumab vedotin (TV) and mirvetuximab soravtansine and can present as blurry vision, dry eye, and corneal abnormalities among other ocular pathologies. Ocular adverse events associated with TV are thought to be an on-target effect related to tissue factor expression in the conjunctiva; mirvetuximab-induced ocular toxicity is an off-target effect caused by the DM4 payload. Use of vascoconstrictor eye drops and cooling eye pads are recommended with TV administration to reduce drug delivery to the eye. Both drugs require prophylactic use of corticosteroid and lubricating eye drops, frequent ophthalmic examinations, and appropriate referral to ophthalmology for new or worsening ocular symptoms [42, 43]. Hepatotoxicity is associated with DM1 and pyrrolobenzodiazepine (PBD) payloads [40, 41]. Pulmonary toxicities including pneumonitis, pneumonia, and respiratory failure were the most common causes of treatment-related death in a recent meta-analysis of 169 clinical trials on ADCs [41]. ADCs associated with pulmonary toxicity include trastuzumab deruxtecan (anti-HER2), tisotumab vedotin (tissue factor-targeting), mirvetuximab soravtansine (anti-folate receptor), and upifitimab rilsodotin (NaPi2b-targeting), all of which are either approved or under investigation for the management of gynecologic cancers as discussed below [44•, 45,46,47]. Low-grade gastrointestinal toxicities including nausea, vomiting, diarrhea, and constipation have been reported with most ADCs but particularly those with a microtubule-inhibitor payload, possibly due to indiscriminate toxicity to rapidly proliferating cells in the GI tract [26]. In general, management of ADC toxicities may involve implementing supportive measures, holding therapy, adjusting the dose, or permanently discontinuing therapy depending on the toxicity type and severity. Given the broad spectrum of toxicities associated with ADCs, careful monitoring and timely recognition and management of adverse events is crucial in preventing morbidity and mortality.

Specific uses of antibody-drug conjugates in gynecologic cancers

Ovary

Over the past decade, targeted therapies including bevacizumab and PARP inhibitors have led to significant advancements in the management of ovarian cancer [9, 48,49,50,51]. Despite these, additional therapies are needed to improve OS and PFS in those with ovarian cancer. ADCs, particularly in the recurrent setting, have shown promising results compared to chemotherapy.

The first ADC approved by the FDA for platinum-resistant recurrent ovarian cancer in November 2022 was mirvetuximab soravtansine (Table 1). Mirvetuximab is composed of an antibody against folate receptor alpha (FRα), a cleavable disulfide linker, and an anti-tubulin DM4 payload. FRα expression is present in over 70% of primary and 80% of recurrent ovarian cancers and is associated with poor response to chemotherapy and shorter disease-free interval [52, 53]. High FRα expression, defined as at least 75% of tumor cells exhibiting at least 2+ membrane staining on the VENTANA FOLR1 immunohistochemistry assay, is present in approximately 35% of platinum-resistant recurrent ovarian cancers. FDA approval of mirvetuximab soravtansine (MIRV) was based on findings from the SORAYA trial, a phase II single-arm study in patients with platinum-resistant ovarian cancer who had received one to three prior lines of therapy, including required prior bevacizumab. Patients with high levels of FRα expression were treated with MIRV monotherapy with an overall response rate (ORR) of 32.4%, with 5% of patients experiencing a complete response. The median duration of response (DOR) was 6.9 months. The most common adverse events were ocular-related events followed by nausea, fatigue, and diarrhea. The treatment discontinuation rate due to adverse events was 9% [54••]. These findings led to accelerated approval of MIRV in patients with FRα-high platinum-resistant ovarian cancer previously treated with 1–3 systemic agents [55]. The MIRASOL trial (NCT04209855) is an active phase III trial comparing MIRV to standard of care chemotherapy in patients with platinum-resistant, advanced high-grade epithelial ovarian cancer. In an initial report presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2023, 453 patients with high FRα expression treated with 1–3 prior lines of treatment were randomized in a 1:1 fashion to MIRV versus standard of care chemotherapy. In this preliminary data, MIRV demonstrated a PFS benefit of 5.62 months versus 3.98 months with chemotherapy and OS benefit of 16.46 months versus 12.75 months with chemotherapy. MIRV demonstrated an ORR of 42.3% and complete response rate of 5.3%. Additionally, compared to chemotherapy, MIRV was associated with lower rates of grade ≥ 3 treatment-emergent adverse events, serious adverse events, and discontinuations due to adverse events [56••].

Table 1 ADCs with FDA accelerated approval in gynecologic cancer
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The combination of MIRV and bevacizumab is listed as a category 2B recommendation in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of FRα-expressing platinum-resistant ovarian cancer based on an ORR of 39% and median PFS of 6.9 months in the phase Ib/II FORWARD trial of heavily pre-treated patients with FRα positivity (≥ 25% of tumor cells with > 2+ intensity by IHC) [57]. In an analysis of expansion cohorts from this trial, ORR was 44% and median PFS was 8.2 months [44•]. Higher FRα expression and lack of prior bevacizumab exposure were associated with higher ORR and longer median PFS, but responses were observed across all subgroups [57].

There are several ongoing trials investigating the use of MIRV in ovarian cancer. The MIROVA trial (NCT04274426) is a phase II study exploring MIRV with carboplatin versus standard of care in FRα-high recurrent platinum-sensitive disease. The PICCOLO trial (NCT05041257) is a phase II study investigating MIRV monotherapy in FRα-high recurrent platinum-sensitive ovarian cancer. The GLORIOSA trial (NCT 05445778) is a phase III randomized trial investigating maintenance MIRV with bevacizumab versus bevacizumab alone in FRα-high platinum-sensitive ovarian cancer.

Luveltamab tazevibulin (known as STRO-002) is a second FRα-targeting ADC composed of a FRα-targeting antibody, a cleavable protease linker, and a 3-aminophenyl-hemiasterlin tubulin-targeting payload which received fast track FDA designation. A phase I trial (NCT03748186) of STRO-002 in patients with heavily pretreated platinum-resistant or refractory ovarian cancer produced an ORR of 32%. The most common adverse event leading to dose reduction or treatment delay was neutropenia [58]. With these encouraging results, the phase II/III REFRaME study is evaluating STRO-002 in patients with platinum-resistant ovarian cancer, and a phase I study (NCT05200364) evaluating STRO-002 plus bevacizumab in patients with recurrent platinum-sensitive or resistant ovarian cancer is currently open for enrollment [59].

Farletuzumab ecteribulin (known as MORAb-202) also targets FRα with a cathepsin cleavable linker and eribulin payload. A phase I study of MORAb-202 monotherapy demonstrated promising results in 22 patients with FRα-positive solid tumors, including 12 patients with previously treated recurrent or metastatic platinum-resistant ovarian cancer. MORAb-202 was well tolerated and resulted in one complete response and six partial responses among patients with ovarian cancer [60]. A phase II study of farletuzumab with carboplatin and taxane in platinum-sensitive ovarian cancer resulted in a 75% ORR [61]. Despite promising results in phase I and II studies, phase III trials did not demonstrate clinical benefit in either platinum-sensitive (NCT00849667) or platinum-resistant (NCT00738699) disease [62]. Nevertheless, an ongoing study (NCT04300556) in patients with platinum-resistant ovarian cancer is evaluating the safety, tolerability, and efficacy of single-agent MORAb-202.

Another promising target of ADCs in ovarian cancer is NaPi2b, a sodium-dependent phosphate transport protein 2B which is expressed in 95% of ovarian cancers [63]. Lifastuzumab vedotin (LIFA) targets NaPi2b with a cleavable linker and a MMAE payload. Phase I studies of LIFA in patients with metastatic platinum-sensitive or platinum-resistant disease have demonstrated encouraging activity with an acceptable safety profile [64•, 65•]. Upifitamab rilsodotin (UpRi) includes a NaPi2B-targeting antibody with novel linker and payload components leading to a high DAR and controlled bystander effect [66]. The single-arm phase Ib/II UPLIFT trial did not meet its primary endpoint of ORR in patients with pre-treated platinum-resistant ovarian cancer [67]. However, two additional trials are investigating the use of UpRi in the recurrent setting: the UPNEXT and UPGRADE-A trials. The UPNEXT phase III trial is investigating the use of UpRi maintenance therapy versus placebo in patients with platinum-sensitive NaPi2b-positive ovarian cancer [68]. The phase I UPGRADE-A trial is a dose-escalation and -expansion study evaluating the use of UpRi with carboplatin in platinum-sensitive ovarian cancer. However, the FDA has paused enrollment due to bleeding events in patients receiving UpRi, including 5/560 (< 1%) patients experiencing grade 5, fatal bleeding events [69].

Lastly, mesothelin is expressed in 55–100% of ovarian cancers and is another target of interest in this patient population [70]. Anetumab ravtansine (AR) is an ADC targeting mesothelin with a disulfide-containing linker and maytansinoid payload. In a randomized phase II study (NCT03587311) in patients with platinum-resistant or refractory ovarian cancer, patients received weekly AR plus bevacizumab versus weekly paclitaxel plus bevacizumab. The study was terminated early as patients receiving weekly paclitaxel and bevacizumab had improved median PFS (9.6 months) compared to those who received AR and bevacizumab (5.3 months) [71]. ADCs in early development for ovarian cancer are summarized in Table 2.

Table 2 Select ADCs under investigation in gynecologic cancer
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Endometrial

Endometrial cancer is the most common gynecologic cancer in the USA [4]. While 85–90% present with early-stage disease often cured by surgery alone, 10–15% present with advanced disease and poor prognosis [3]. Immune checkpoint inhibitors have become a promising therapy for patients with endometrial cancer in various settings. Pembrolizumab and dostarlimab, monoclonal antibodies against PD-1, have been approved by the FDA for patients with advanced or recurrent endometrial cancer and advanced or recurrent dMMR/MSI-H solid tumors [17, 19]. While there are several promising ADCs under investigation for endometrial cancer, none are currently FDA approved.

Human epidermal growth factor receptor 2 (HER2) is expressed in ~ 30% of high grade serous uterine cancers and is a target of interest for therapy. Trastuzumab deruxtecan (T-DXd) is an ADC composed of trastuzumab (anti-HER2 antibody), a cleavable linker, and DXd payload. The STATICE trial investigated the use of trastuzumab deruxtecan in patients with HER2-expressing uterine carcinosarcoma and found an ORR of 54.5% in the HER2-high and 70% in the HER-2 low groups, demonstrating efficacy regardless of the degree of HER2 expression [72••]. T-DXd is being investigated in several ongoing trials, either alone (DESTINY-PanTumor02 trial, NCT04482309) or in combination with a PARP inhibitor (NCT04585958) for patients with HER-2 expressing endometrial cancer. Interim results from the DESTINY-PanTumor02 study were recently presented at the 2023 ASCO Annual Meeting. T-DXd demonstrated an ORR of 57.5% in patients with endometrial cancer, and the median DOR was not reached [73••]. DB-1303 is an additional ADC targeting HER2 with a cleavable linker and a topoisomerase I inhibitor P1003 payload. Based on promising preliminary results in patients with HER2-positive or HER2-low solid tumors, the FDA granted fast track designation for DB-1303 for treatment of advanced or metastatic HER2-expressing endometrial cancers. An ongoing phase I/IIa trial (NCT05150691) is evaluating the safety and tolerability of DB-1303 in this population.

FRα is expressed in 64% of endometrial cancers, and ADCs under investigation which target FRα include MIRV and STRO-002 [74]. In a phase I dose-escalation study of MIRV in patients with FRα-positive tumors, 2 of 11 patients with endometrial cancer exhibited partial response [75]. A phase II study of MIRV and pembrolizumab in patients with microsatellite stable recurrent or persistent endometrial cancer (NCT03835819) is ongoing. STRO-002 is also being investigated in a phase I study in patients with recurrent or progressive endometrial cancer (NCT03748186).

Lastly, tumor-associated calcium signal transducer (Trop-2) is expressed in 65-95% of endometrial cancers [76]. Sacituzumab govitecan (IMMU-132) is an anti-Trop-2 monoclonal antibody with a cleavable CLA2 linker and SN-38 payload, the active metabolite of irinotecan [77]. In a phase I/II basket trial of patients with metastatic endometrial cancer who progressed after at least 1 prior systemic therapy, IMMU-132 resulted in an ORR of 22.2%. The most frequent treatment-related adverse events were nausea, diarrhea, neutropenia, alopecia, and fatigue with infrequent grade 3 or higher events [78].

Cervix

Despite an overall decline in the incidence of cervical cancer in the USA, there has been an increase in the incidence of stage IV cervical cancers over the last two decades [79, 80]. The 5-year survival rate in this population is around 17% [4]. Primary treatment in patients with advanced-stage cervical cancer often includes a combination of chemotherapy and radiation therapy. In patients with recurrent, persistent, or metastatic cervical cancer, the addition of bevacizumab to standard chemotherapy resulted in improved response rates and OS [11]. More recently, pembrolizumab demonstrated improved PFS and OS in patients with persistent, recurrent, or metastatic cervical cancer [20]. Currently, one ADC is FDA-approved for the management of cervical cancer.

Tissue factor (TF) is expressed in 90–100% of cervical cancers [81]. Tisotumab vedotin (TV) targets TF and contains a protease-cleavable linker and a microtubule disruptor payload, MMAE (Table 1). FDA accelerated approval of TV was supported by results from the innovaTV 204 trial. In this multicenter, single arm phase II study, 102 patients with previously treated recurrent or metastatic cervical cancer who received tisotumab vedotin had an ORR of 24% with 7% complete response and 17% partial response. The median DOR was 8.3 months, median PFS was 4.2 months, and median OS was 12.1 months. TV was overall well tolerated; the most frequent treatment-related adverse events were alopecia, epistaxis, nausea, fatigue, conjunctivitis, and xerophthalmia [82••]. Recently published results from the phase Ib/II trial, ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081) revealed that the combination of TV with either carboplatin, bevacizumab, or pembrolizumab demonstrated encouraging antitumor activity and safety profiles in patients with recurrent or stage IVB cervical cancer. In the dose-escalation arms, there were no dose-limiting toxicities observed. In the dose expansion arms, the ORR was 54.5% in the TV plus carboplatin group with a median DOR of 8.6 months. The ORR was 40.6% in the TV plus pembrolizumab as first-line treatment group; the median DOR was not reached. Lastly, the ORR was 35.3% in the TV plus pembrolizumab as second-/third-line treatment group with a median DOR of 14.1 months. The most common grade 3 or higher adverse events were anemia, diarrhea, nausea, and thrombocytopenia [83••]. The phase III innovaTV 301 (NCT04697628) is evaluating the effect of TV versus investigator choice chemotherapy in patients with previously treated recurrent or metastatic cervical cancer. A recent press release announced that TV achieved significant improvement in OS, meeting the primary end point of the phase 3 innovaTV 301 trial. TV also resulted in significant improvement in the secondary end points of PFS and ORR [84].

Targeting HER2 with T-DXd has demonstrated promising results in early studies. DESTINY-PanTumor02 is a phase II study of T-DXd in patents with HER2-expressing solid tumors. Interim results recently presented revealed an ORR of 50% in patients with cervical cancer. The most common treatment-related adverse events were nausea, fatigue, and cytopenia [85]. A phase I/IIa trial (NCT04644068) is investigating the use of T-DXd and a PARP inhibitor in patients with cervical cancer.

Mechanisms of ADC resistance

While ADCs have provided an opportunity for improved management of gynecologic cancers, mechanisms of ADC resistance remain an area of concern. Resistance mechanisms are thought to be multifactorial, involving alterations in antigen expression, ADC processing, and tumor sensitivity to the payload. Downregulation of the target antigen can lead to resistance due to decreased antibody binding. For example, in patients with HER2+ breast cancer, treatment with the ADC trastuzumab emtansine led to decreased tumor antigen expression of HER2 over time and subsequent resistance to the ADC [86]. Trastuzumab deruxtecan, an ADC which is structurally different from trastuzumab emtansine, is effective against tumors that are resistant to trastuzumab emtansine partly due to its ability to exert the bystander effect. For example, tumor cells which have developed resistance to trastuzumab emtansine by decreasing expression of HER2 are susceptible to trastuzumab deruxtecan if located near HER2-expressing tumor cells [87]. This bystander effect may explain the efficacy of trastuzumab deruxtecan in uterine carcinosarcoma regardless of HER2 status.

Changes in ADC uptake and intracellular processing can also contribute to resistance. Uptake of the ADC may be inhibited by formation of basement membrane barriers, and processing may be inhibited by reduction in transport and processing proteins or absence of proteolytic activity which inhibits lysosomal degradation [88,89,90]. Lastly, ADC resistance may occur due to decreased tumor sensitivity to the payload. For example, changes in the expression of a topoisomerase may lead to resistance to ADCs with topoisomerase inhibitor payloads [88]. Alternatively, tumors may upregulate expression of ATP-binding cassette (ABC) transporter proteins, resulting in increased efflux of the payload. It is hypothesized that T-DXd’s efficacy against tumors resistant to trastuzumab emtansine is not only due to the bystander effect, but also because it incorporates the DXd payload instead of DM1, which has a different mechanism of action and is less susceptible to ABC transporter proteins [24].

Conclusion

ADCs represent a novel approach to the management of gynecologic cancers, and additional trials are underway to identify agents with demonstrated efficacy in gynecologic cancers, particularly in the metastatic and recurrent settings in which treatment options are limited. In general, ADCs exhibit less toxicity compared to standard chemotherapy regimens with improved efficacy. Despite this, unique toxicities are noted with ADCs, and prophylaxis, monitoring, and prompt evaluation and management must be considered throughout treatment. While most agents have been studied as monotherapy, combination regimen strategies are being considered and may provide more durable responses, though at the risk of cumulative toxicity. Mechanisms of resistance are not yet fully understood and warrant further investigation. ADCs have emerged as promising therapeutic agents for patients with gynecologic cancers, and current and future investigations of ADCs may further improve oncologic outcomes while limiting treatment toxicities.