Background

Gynecological cancers are one of the most common cancers in women irrespective of geography and continue to pose significant challenges to women’s health worldwide. Treatment of gynecologic cancers is becoming more targeted with biomarker-directed therapy, which is associated with improved outcomes. Despite this, for many patients who present with advanced or recurrent disease, no definitive cure is possible, and gynecological cancer remains a critical area of unmet need. Advances in targeted therapies, immunologic treatments, antibody–drug conjugates, and local therapy in different therapeutic settings: both in early and in the recurrent/metastatic setting are offering new hope and improved outcomes for patients at different timepoints in a patient’s journey.

In this editorial, we provide a brief summary of key study results presented at the American Society of Clinical Oncology (ASCO) 2023 for gynecological cancers.

Ovarian Cancer (OC)

For patients with high-grade epithelial ovarian cancer, significant advances have been made in surgery, adjuvant therapy, and the incorporation of targeted and maintenance treatments. Within the past several years, the approval of three poly-adenosine diphosphate (ADP) ribose inhibitors (PARPi), incorporation of bevacizumab, and most recently, approval of the first antibody–drug conjugate (ADC) mirvetuximab soravtansine-gynx (ElahereTM), which targets folate receptor-α, have contributed to improved response rates and survival. Despite this, patients with high-grade epithelial ovarian cancer continue to have the highest mortality rate among gynecological malignancies. The relative combined (for all stages and for all types) 5-year survival rate for patients with newly diagnosed ovarian cancer was about 50% between 2012 and 2018 [2, 3]. For comparison, the 5-year relative survival rate between 2012 and 2018 for cervical cancer was 67%, and for endometrial cancer it was 84% [3,4,5].

Until the approval of mirvetuximab soravtansine-gynx in late 2022, the only successfully approved targeted therapies for patients with epithelial ovarian cancer included bevacizumab and PARP inhibitors. PARP inhibitors have transformed the therapeutic landscape in epithelial ovarian cancer over the past decade, especially as a maintenance/treatment option after frontline therapy, demonstrating benefit regardless of BRCA mutation or homologous recombination status [6,7,8]. However, with mature data in recurrent disease, detrimental survival results led to the withdrawals in 2022 of previously approved PARP inhibitors in the most advanced settings’ indication (as monotherapy in third or subsequent lines) by the US Food and Drug Administration (FDA) [9]. Two other indications, as maintenance after platinum-sensitive relapse, were also restricted [9, 10].

This evolution of approvals and recent reevaluations has reignited the search for novel molecular biomarkers and targeted treatment, especially in the platinum-resistant setting. Here, we present updates from recently presented clinical trials.

Two Phase III Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Studies in Patients with Ovarian Cancer

Complete tumor resection to no gross residual disease at upfront or interval cytoreductive surgery is the most important prognostic factor for patients with advanced epithelial ovarian cancer. Given the peritoneal dissemination of most advanced stage epithelial ovarian cancers, the administration of adjuvant intraperitoneal chemotherapy has historically yielded promising results [11]. More recently, the incorporation of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreduction has been evaluated in multiple clinical trials [12]. However, operational challenges and personnel with expertise at surgical centers have prevented widespread uptake, especially given the increased potential for toxicity.

Results from two phase III trials investigating HIPEC in epithelial ovarian cancers were presented at ASCO 2023. The randomized phase III OVHIPEC-1 trial investigated the addition of HIPEC to interval cytoreductive surgery in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. Patients received three cycles of neoadjuvant treatment with carboplatin and paclitaxel before the surgery and then three cycles of adjuvant treatment after the surgery. Patients were randomized to receive interval cytoreductive surgery with HIPEC (cisplatin 100 mg/m2 intraperitoneally over 90 min at 42 °C) or without HIPEC. Randomization was performed at the time of surgery when either complete (no visible disease) or optimal cytoreduction (residual tumor measuring < 10 mm in diameter) was anticipated. The benefit of HIPEC was confirmed by final survival analysis after a 10 year follow-up. Median recurrence-free survival was significantly longer in a group of patients who received HIPEC at the time of surgery compared with the control arm: 14.3 versuss 10.7 months, respectively [hazard ratio (HR) 0.63; 95% confidence interval (CI), 0.48–0.83; stratified P < 0.001]. Significant improvement was reported for overall survival: 44.9 months versus 33.3 months (HR 0.70; 95% CI 0.53–0.92; stratified P = 0.011), respectively. It is notable that there was no imbalance in subsequent therapy after disease recurrence that could explain the improved overall survival after HIPEC. Subsequent anticancer therapies that included chemotherapy (platinum- and non-platinum-based), secondary surgery, PARP inhibitors, and bevacizumab, were received by 104 patients (84.6%) in the surgery group and 100 patients (82.0%) in the surgery-plus-HIPEC group. The median number of subsequent systemic treatment lines was 2 [interquartile range (IQR) 1–3] in both arms [13].

For patients with recurrent epithelial ovarian cancer (EOC), the incorporation of HIPEC was explored in a phase III randomized clinical trial (CHIPOR). This multicentric randomized phase III trial was conducted in 31 institutions and enrolled 415 patients with a first platinum-sensitive relapse (platinum-free interval of ≥ 6 months) epithelial ovarian cancer. Patients received 6 cycles of platinum and taxane-based chemotherapy, with or without bevacizumab, and those amenable to a complete cytoreductive surgery at the end of chemotherapy were enrolled and randomly assigned to receive HIPEC (cisplatin 75 mg/m2 at 41 °C for 60 min) or not. The results demonstrated that HIPEC significantly improves overall survival (OS) and peritoneal progression-free survival (PFS) of women with first platinum-sensitive relapse of EOC treated with second-line platinum-based chemotherapy (CT) followed by secondary complete cytoreductive surgery. Median overall survival significantly increased in HIPEC arm versus non-HIPEC arm: 54.3 months versus 45.8 months (HR 0.69; 95% CI 0.5–0.94; stratified P = 0.02). Median peritoneal PFS also increased [14].

Both studies reported no change in adverse event (AE) rate or delayed start of adjuvant CT. The percentage of patients who had grade 3 or 4 AE in the OVHIPEC study was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P = 0.76) [15]. Results for the CHIPOR trial reported postoperative grade 3 or 4 AE in 15% and in 11% of patients in HIPEC and non-HIPEC arms, respectively [14].

HIPEC, when added to optimal cytoreductive surgery, appears to have a beneficial effect on the survival outcomes of patients with advanced stage ovarian cancer following neoadjuvant chemotherapy; however, the question remains regarding whether it is beneficial following primary cytoreduction surgery. There are prospective clinical studies evaluating the role of HIPEC in the primary treatment setting [16].

Phase III Studies in Patients with Ovarian Cancer

Several anticipated phase III study results were presented, one of which was an interim PFS analysis of the DUO-O trial that incorporates a checkpoint inhibitor with a PARP inhibitor. Triple maintenance therapy with bevacizumab, olaparib, and durvalumab improved progression-free survival in patients with newly diagnosed advanced stage epithelial ovarian cancer without tumor BRCA mutation compared with patients receiving maintenance with bevacizumab monotherapy. Even though maintenance therapy with olaparib with and without bevacizumab has improved outcomes for patients with epithelial ovarian cancer in the frontline setting [8, 17], unmet needs still remain, especially in patients without BRCA mutations. The study rationale was based on the assumption that a triple combination of an immune checkpoint inhibitor with an antiangiogenic agent and a PARP inhibitor may enhance the antitumor effect [18].

The interim analysis demonstrated that DUO-O met its primary endpoint of PFS in the selected population. Results showed that the risk of radiographic progression was significantly reduced, with a HR 0.49 (95% CI 0.34–0.69; P < 0.0001) and HR 0.63 (95% CI 0.52–0.76; P < 0.0001) in the homologous recombination deficiency positive (HRD+) and intention-to-treat populations, respectively. For HRD+ patients, PFS was 37.3 months versus 23 months for those in the standard-of-care arm. PFS benefit was also observed in HRD population, with 17.4 months in control arm versus 20.9 months in the triple therapy arm (HR 0.68; 95% CI 0.54–0.86), a population that did not show benefit of bevacizumab + olaparib versus bevacizumab in PAOLA-1 trial. Unfortunately, the study lacked the control arm to isolate the effect of durvalumab, and therefore did not allow the individual contribution of olaparib and bevacizumab combination. The trial is ongoing, and the final results of the study are yet to be reported [19].

Antibody–drug conjugates are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell-killing properties of chemotherapy. A rapidly growing class of oncologic therapeutics, antibody–drug conjugates (ADCs) showed positive results in multiple tumors and are widely explored in oncological studies [20].

Mirvetuximab soravtansine received accelerated FDA approval in the fall of 2022 after meaningful antitumor activity was demonstrated in the single-arm SORAYA trial in platinum-resistant ovarian cancer [21]. Positive results from the anticipated international confirmatory phase III MIRASOL randomized clinical trial were presented as a late-breaking abstract at ASCO 2023.

The phase III trial MIRASOL (GOG 3045/ENGOT-ov55) studied mirvetuximab soravtansine compared with chemotherapy in patients with platinum-resistant high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-α expression, who received one to three prior lines of treatment. A total of 453 patients with platinum-resistant, high folate receptor alpha (FRα) expression cancer were randomized 1:1 to mirvetuximab soravtansine (MIRV) or chemotherapy by investigator’s choice (IC): paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was progression-free survival (PFS) by the investigator (INV), with key secondary endpoints of objective response rate (ORR) and overall survival (OS).

The study met its primary and key secondary endpoints with statistically significant improvement of PFS based on HR 0.64 and 0.66 in the bevacizumab-pretreated population and bevacizumab-naïve population, respectively, and improvement of OS based on HR 0.74 and 0.51 in the same subgroups, respectively. The overall response rate was significantly higher in MIRV arm by investigator’s evaluation: 42.3% versus 5.9%, P < 0.0001, and by blinded independent central review (BICR): 36.1% versus 14.6%, P < 0.0001. Mirvetuximab treatment was well tolerated, with lower rate of treatment-related grade ≥ 3 AE (42% versus 54%) in mirvetuximab arm compared with investigator’s choice (IC) treatment.

The significance of this approval and trial remains that MIRV is the first treatment to demonstrate a PFS and OS benefit in patients with platinum-resistant ovarian cancer. This efficacy data, along with the favorable safety profile, position MIRV as a new standard of care for patients with FRα-positive platinum-resistance ovarian cancer [22].

Mirvetuximab soravtansine (MIRV) is an ADC containing a FRα-binding antibody, a cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent.

Folate receptor alpha (FRα) has emerged as an attractive candidate for molecularly targeted approaches since aberrant overexpression of FRα is characteristic of a variety of epithelial tumors, including ovarian carcinoma [23]. About 80% of epithelial ovarian cancer (EOC) express FRα, while there is no expression in normal ovarian epithelium [24, 25]. Analysis of diverse histotypes of ovarian cancer tissue showed membrane and/or cytoplasmic FRα staining in 52.7% of tumors from 316 patients with ovarian cancer [26]. This makes folate receptor alpha (FRα) a rational therapeutic target in ovarian cancer [25, 27].

To date, efficacy for mirvetuximab soravtansine has been shown with patients who have FRα high expression; however, some patients with low to moderate expression have been shown to also have a response. The biomarker could be defined by VENTANA FOLR1 (FOLR1-2.1) RxDx assay, the first immunohistochemistry (IHC) companion diagnostic test to help identify patients with epithelial ovarian cancer who are eligible for treatment with mirvetuximab soravtansine [28]. Future studies will evaluate thresholds of the biomarker and whether the incorporation of mirvetuximab into earlier lines of therapy can benefit patients sooner.

Phase III Ongoing Studies in OC

Multiple studies of novel ADC and novel immunotherapy agents in ovarian cancer are underway, and below is a list of selected phase III trials:

  • A phase III study (UP-NEXT) of a NaPi2b-directed antibody–drug conjugate (ADC), upitifamab rilsodotin (UpRi), targeting a sodium-dependent phosphate transporter protein NaPi2b that is broadly expressed in high-grade serous ovarian cancer (HGSOC), is designed in platinum-sensitive recurrent ovarian cancer [29].

  • A phase III study GLORIOSA designed to evaluate the efficacy of the ADC mirvetuximab soravtansine with bevacizumab in platinum-sensitive patients in the second line setting [30].

  • A phase III ARTISTRY-7 study intends to evaluate the novel engineered cytokine nemvaleukin alpha (nemvaleukin, ALKS 4230) in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in recurrent setting [31].

  • A phase III study FLORA-5 study has been designed to assess the safety and efficacy of oregovomab, a novel immunotherapy that enhances the immune response to CA-125, in the front-line setting in optimally debulked patients with FIGO III/IV EOC and serum CA125 ≥ 50 U/ml [32].

Cervical Cancer

Cervical cancer, a largely preventable cancer, has witnessed a decrease in incidence over the last 20 years through effective screening and vaccination against human papillomavirus (HPV) in developed countries [33,34,35]. Recent research on the molecular and immune mechanisms in HPV-associated cervical cancer paves the way for immunotherapies for the treatment of cervical cancer.

Most patients present with early disease and are cured, and the 5-year survival rate for localized disease is up to 91%, while for the regionally advanced disease it is 60% and it is only 19% for patients with distant metastases (data originally published by the National Cancer Institute, updated April 2023) [36].

Phase III Studies in Cervical Cancer

For patients with early-stage disease amenable to surgical treatment, radical hysterectomy is highly effective. However, radical surgery increases a patient’s risk of long-term morbidity, including bowel and bladder incontinence, fistula, and dysfunction [37].

The international randomized Gynecologic Cancer Intergroup phase III study led by the Canadian Cancer Trials Group (CCTG CX.5-SHAPE) was designed to compare radical hysterectomy and pelvic node dissection versus simple hysterectomy and pelvic node dissection in patients with low-risk early-stage cervical cancer (CC). The hypothesis was that less radical surgery may be a safer option associated with decreased morbidity due to postsurgical complications. Eligible patients included those with stage 1A2 or 1B1 cervical cancer with lesion ≤ 2 cm and randomized to radical hysterectomy and pelvic node dissection versus simple hysterectomy and pelvic node dissection. The primary endpoint was pelvic recurrence rate at 3 years. Results from over 700 enrolled patients indicated that the pelvic recurrence rate at 3 years in women with low-risk early-stage cervical cancer who underwent a simple hysterectomy is not inferior to those who received a radical hysterectomy. Fewer surgical complications and better quality of life were observed with patients who underwent simple hysterectomy. This study confirmed that following adequate preoperative assessment, simple hysterectomy can now be considered for patients with low-risk early-stage cervical cancer [38].

For patients with advanced and recurrent cervical cancer, the incorporation of checkpoint inhibitors has improved outcomes and transformed the standard of care after the results for Keynote 826 were presented. This phase III clinical trial evaluated the addition of pembrolizumab to platinum-based chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Patients treated with pembrolizumab had a significantly reduced risk of death by 40% in the programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 population, by 37% in the all-comer population, and by 42% in the CPS ≥ 10 population with manageable safety profiles. Based on these study results in the National Comprehensive Cancer Network (NCCN) guidelines, this therapy was moved to the first line in the recurrent or metastatic disease setting. At this ASCO, updated results of Keynote 826 confirmed survival benefits with the addition of pembrolizumab to chemotherapy with no new safety signals after more than 3 years of follow-up [39].

FDA-approved ADC, tisotumab vedotin, which targets tissue factor (TF), frequently overexpressed in cervical cancer, was discussed during an oral session on ADCs in gynecologic cancers. Tisotumab vedotin (TV) was the first ADC to receive FDA approval (in September 2021) in gynecologic cancer, based on the phase II InnovaTV 204 trial, in which the ADC showed a confirmed objective response rate of 24% among 102 patients with previously treated recurrent or metastatic cervical cancer [40]. The ongoing randomized, open-label phase III InnovaTV-301 trial will assess the effect of TV in pretreated recurrent or metastatic cervical cancer. Meanwhile, tisotumab vedotin, in combination with chemotherapy and other targeted agents, is currently being evaluated [41].

Early-Phase Cervical Cancer Trials

Some of the early-phase cervical cancer studies presented at ASCO with promising results are listed below:

  • The first in human (FIH) study of SHR-1701, a novel bifunctional fusion protein targeting PD-L1 and transforming growth factor (TGF) beta receptor inhibitor with standard of care (SoC) platinum-based chemotherapy and BP102 (a bevacizumab biosimilar), for persistent, recurrent, or metastatic CC [42].

  • A phase II study investigated novel programmed cell death (PD-1) inhibitor camrelizumab as part of neoadjuvant treatment for locally advanced CC [43].

  • A phase I Colibri trial studied how a dual neoadjuvant combination of PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) inhibitors (nivolumab + ipilimumab) impacted immune response in CC [44].

Endometrial Cancer

Endometrial cancer (EC) is the sixth most common cancer in women worldwide, with over 400,000 new cases reported in 2020 [45].

Its incidence and mortality rate have both been rising in the last decade. An ageing population may have contributed to this trend, along with the growing prevalence of obesity. It is surmised that among all malignancies, endometrial cancer has the strongest association with obesity. A worrying trend is the higher rate of increase of endometrial cancer and, especially, of tumors with aggressive non-endometrioid histologic features, which have been associated with poorer outcomes, among Black women [46, 47].

The incorporation of molecular classification into diagnostics (staging), risk assessment and treatment decisions have been increasingly adopted as additional data have become available [48,49,50]. The combination of chemotherapy with platinum-based therapy has long been the standard treatment for women with advanced or recurrent endometrial cancer. Treatment options for patients with recurrent disease to date have included the incorporation of checkpoint blockade alone [for patients with microsatellite instability (MSI-H) or deficient mismatch repair tumors] or in combination with lenvatinib (for patients with microsatellite stable tumors). Newer data have evaluated the incorporation of checkpoint blockade in the front-line setting.

Results of Phase III Studies for Endometrial Cancer Treatment

RUBY (ENGOT-EN6-NSGO/GOG-3031/RUBY) phase III trial evaluated the efficacy and safety of the antiprogrammed death 1 (PD-1) dostarlimab + standard of care carboplatin–paclitaxel (CP) versus CP alone in patients with advanced or recurrent endometrial cancer. The results of the primary endpoint of PFS by investigator assessment per RECIST v1.1, published in March 2023, showed that PFS was significantly longer with dostarlimab + chemotherapy than placebo + chemotherapy in the mismatch repair deficient/microsatellite instability high (dMMR/MSI-H; HR 0.28) and overall populations (HR 0.64) [51]. At ASCO 2023 the secondary efficacy endpoints by blinded independent central review (BICR) were presented and these results confirmed previously reported primary endpoint results: radiographic PFS by BICR was longer with dostarlimab + CP arm compared with placebo + CP in the dMMR/MSI-H (HR 0.29; 95% CI 0.158–0.543) and overall populations (HR 0.66; 95% CI 0.517–0.853) [52].

The study confirmed the hypothesis that dostarlimab in combination with standard chemotherapy will improve outcomes in dMMR/MSI-H and the overall population with primary advanced stage III or IV or first recurrent EC.

Patient-reported outcomes (PRO) for this study population were also presented at ASCO 2023. PROs assessments measure the experience related to an intervention from the patient’s perspective and are increasingly assessed in clinical trials as a measure of effectiveness. The results of RUBY trial showed that patient-reported outcomes were similar for two arms through the chemo period (until cycle 7) and the following 3-year period. In conclusion, dostarlimab + chemotherapy significantly improved PFS while maintaining health-related quality of life, further supporting its use as a standard of care in primary advanced/recurrent EC [53].

On July 31, 2023, FDA approved dostarlimab-gxly (Jemperli®, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or EC that is microsatellite instability-high (MSI-H) [54].

Early Phase Endometrial Cancer Studies

An alternative to commonly used hormonal therapies was evaluated in the open-label multicenter investigator-initiated non-randomized phase II OATH study. This trial investigated the potential of dual hormonal blockade through the combination of antiprogesterone [onapristone (ONA)] and antiestrogen therapy [anastrazol (ANA)]. Initial results of 14 patients evaluated as of 20 January 20 2023, showed a favorable safety profile of the studied combination, with mainly grade 1 or 2 AEs. The most common treatment-related AEs were hot flashes (36%), which is expected for this treatment. Preliminary efficacy results of dual hormonal blockade using ONA and ANA in heavily pretreated patients with EC suggest that this combination of ONA + ANA has promising activity and is well tolerated [55].

An open-label single-arm phase II trial investigated antitumor activity and safety of combination of immunological drug (camrelizumab, a humanized anti-PD-1 monoclonal antibody) and vascular-targeted agent (apatinib, a highly selective vascular endothelial growth factor receptor 2 inhibitor) in 36 patients with advanced or recurrent endometrial cancer in the second line setting. The confirmed objective response rate was 44.4% and the confirmed disease control rate was 88.9% (95% CI 73.9–96.9%), with two complete responses (5.6%), 14 partial responses (38.9%), and 16 stable diseases (47.2%). Median duration of response was 9.9 months [95% CI: 4.2–not reached (NR)], median PFS was 6.4 months (95% CI 5.3–13), and median OS was 21.0 months (95% CI 14–NR) [56].

The preliminary results of open-label phase II trial that studied ADC sacituzumab govitecan in patients with recurrent endometrial cancer with Trop-2 overexpression showed that in 20 patients with ≥ 13 weeks of follow-up evaluable for response, ORR was 35% with one complete response (5.0%) and 6 partial responses (30%). In addition, stable disease was reported in 50% [57]. The antibody–drug conjugate, sacituzumab govitecan, targets trophoblast cell surface antigen-2 (Trop-2)—a cell surface glycoprotein highly expressed in many epithelial tumors—and delivers the active metabolite of irinotecan SN-38 to Trop-2-positive tumor cells.

In conclusion, there is a large wave of ongoing clinical trials of targeted therapies and their combinations in endometrial cancer. Further molecular investigation and translational exploratory analysis will be very important to identify new potential predictive and prognostic factors in this population with limited therapeutic options in advanced stages.

Solid Tumor Trials with Gynecologic Cancers Cohorts

Several early-phase trials for different solid tumors reported promising efficacy results for gynecologic tumors that could support further research for these cancer subtypes. We would like to provide a summary of two trials investigating ADCs.

The study DESTINY-PanTumor02 (DP-02) presented an interim analysis of the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2) expressing solid tumors not amenable to curative therapy. T-DXd is an antibody–drug conjugate targeting HER2 and is approved in HER2-expressing breast and gastric cancers. This open-labeled study enrolled patients with HER2-expressing (IHC 3+ or IHC 2+ by local or central testing) locally advanced or metastatic disease that progressed after more than one systemic treatment or that has no other treatment options. Cohorts included patients with biliary tract, bladder, cervical, endometrial, ovarian, or pancreatic tumors, or other tumors (excluding breast, gastric, colorectal, and non-small cell lung cancer). The primary endpoint was investigator-assessed confirmed objective response rate (ORR). At data cutoff (16 November 2022), 267 patients had been evaluated and the total ORR was 37.1%. Responses were especially high among patients who had cervical, endometrial, and ovarian cancer—50.0%, 57.5%, and 45.0%, respectively. In gynecologic tumor cohorts, responses were higher in patients with HER2 IHC 3+ compared with those with HER2 IHC 2+: 84.6% versus 47.1%, 75% versus 40%, and 63.6% versus 36.8% in endometrial, cervical, and ovarian cancer, respectively. These interim results show that T-DXd with topoisomerase I inhibitor payload could be a potential new treatment option for patients with HER2-expressing gynecological tumors [58].

The phase II basket study TROPiCS-03 was designed to evaluate sacituzumab govitecan in patients with metastatic solid tumors. At ASCO 2023, it presented early analysis in patients with advanced/metastatic endometrial cancer who progressed on or after platinum-based and anti-PD-(L)1 therapy.

The results showed that in 20 patients with ≥ 13 weeks of follow-up, ORR was 25% and all responses were partial responses. In addition, stable disease was reported in 40% and progressive disease was reported in 15% of patients. Treatment was ongoing for 50% of patients. Grade ≥ 3 treatment-related AEs occurred in 64% of patients, but the discontinuation rate was 7%. Preliminary findings showed encouraging efficacy of SG, with a manageable toxicity profile in a pretreated population with advanced/metastatic endometrial cancer [59].

Conclusions

This summary of presented trials showed that the search for different combinations and targeted therapies with predictive biomarkers and favorable safety profiles is paramount to improve outcomes in patients with gynecologic cancers at different time points in a patient’s journey [60].

Recent approvals showed that the treatment of gynecologic cancers is becoming more targeted, and the variety of selected oncogene targets is expanding with the introduction of biomarker-directed therapy for different cancer subtypes.

ADCs represent the next area of research toward personalized therapy in gynecologic cancer. ADC development requires the identification of appropriate tumor-associated antigens that can be targeted by the ADC to effectively kill cancer cells while minimizing damage to healthy cells, thus limiting systemic toxicities.

Immunotherapy is another area of dynamic investigation, and it is now being explored in front-line settings as monotherapy and in combination with other targeted therapies. Treatment with immunotherapies can achieve impressive and durable success and thus novel drugs and different combinations need to be further investigated.

Therapeutic and diagnostic advances have an impact on the traditional surgical treatment of gynecological cancers. Implementation of new approaches like HIPEC in ovarian cancer or deescalating surgical intervention in selected patients with cervical and endometrial cancer significantly improves both oncological and surgical outcomes.

The main challenges in clinical practice remain to manage advanced stages of the disease, to prevent/overcome resistance to treatments, and to manage treatment-related AEs, thus improving treatment compliance and health-related quality of life for these patients.