Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.

The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear. This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital’s ethics committee (approval number: MH2022-093). This study enrolled 20 patients, who underwent a median follow-up of 17.8 months (95% confidence interval: 16.6–18.9). The best overall response rate was 60.0% (36.1–80.9), and the median progression-free survival was 11.6 months (2.9–20.3). The median progression-free survival in the p53 abnormal group (n = 9) was 3.4 months (3.0–3.8); however, progression-free survival did not reach the median (P < 0.001) in the mismatch repair-deficient/no specific molecular profile group (n = 11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred. The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.

Objective: To compare real-world PFS between BEV and OLA as maintenance therapy for PSROC, with an exploratory evaluation of clinical outcomes after OLA dose reduction. Methods: This retrospective multicenter study included 101 patients with first platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer who achieved a response to platinum-based chemotherapy and then received maintenance therapy. Patients were classified into three groups: BEV (n = 34), standard-dose OLA (n = 31), and dose-reduced OLA (n = 36). The primary endpoint was PFS; secondary endpoints were OS and adverse events. Survival outcomes were evaluated using Kaplan–Meier methods and Cox proportional hazards models. Results: In the primary comparison of all OLA-treated patients versus BEV, OLA was associated with longer PFS (HR 0.48, 95% CI 0.29–0.77), with median PFS of 19 months versus 16 months, respectively. OS did not differ significantly between groups (HR 0.60, 95% CI 0.34–1.05). In exploratory subgroup analyses, patients who underwent OLA dose reduction had numerically longer PFS than those who remained on the full dose; however, this comparison is vulnerable to time-dependent and selection biases and should be interpreted cautiously. Grade ≥ 3 hematologic toxicities were more frequent in the OLA groups but were clinically manageable. Conclusions: In real-world practice, OLA was associated with longer PFS than BEV in PSROC. Clinically necessary dose reduction appeared feasible without an obvious loss of benefit, although this finding requires cautious interpretation.

Objective: Bevacizumab (BEV) and Olaparib (OLA) have demonstrated clinical efficacy as maintenance therapies for first platinum-sensitive recurrent ovarian cancer. However, direct comparisons between these agents independent of homologous recombination deficiency (HRD) and BRCA status, remain limited and the clinical validity of OLA dose reduction has not yet been confirmed. This study aimed to compare the efficacy and safety of BEV, standard-dose OLA, and dose-reduced OLA as maintenance therapy and to evaluate the clinical utility of OLA dose reduction. Methods: This retrospective multicenter study included 101 patients with first platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer who received maintenance therapy after achieving a response to chemotherapy. Patients were classified into three groups: BEV (n = 34), standard-dose OLA (n = 31), and dose-reduced OLA (n = 36). The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and adverse events. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: Median PFS was 16 months in the BEV group, 16 months in the standard-dose OLA group, and 24 months in the dose-reduced OLA group, with significantly longer PFS in the dose-reduced OLA group (p < 0.001). In the multivariate Cox analysis, treatment remained an independent prognostic factor for PFS (HR 0.67, 95% CI 0.46–0.96, p = 0.030). Median OS was 44, 45, and 64 months, respectively, with no significant differences among groups; PFI ≥12 months was the only independent prognostic factor for OS. Grade ≥3 hematologic toxicities were more frequent in the OLA groups but were manageable. Conclusions: Dose-reduced OLA was associated with prolonged PFS while maintaining manageable toxicity, supporting its clinical validity as a maintenance option independent of HRD and BRCA status.

Background: The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has identified four risk groups for the prognosis of endometrial cancer (EC). However, the prognostic impact of these subgroups on lenvatinib (LEN) plus pembrolizumab (PEM) administered as subsequent therapy after relapse is unknown. This study aimed to explore the effectiveness and safety of LEN/PEM therapy for recurrent EC using the ProMisE molecular classification. Methods:This single-center retrospective study included patients who underwent LEN/PEM therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP) subtypes using immunohistochemistry (IHC). The response rate, progression-free survival (PFS), and adverse events were evaluated using electronic medical records. The study was approved by the hospital’s ethics committee (approval number: MH2022-093). Results: This study enrolled 20 patients, who underwent a median follow-up of 10.7 months [95% confidence interval (CI): 8.9-12.4]. The best overall response rate was 60.0% (36.1–80.9) and the median PFS was 9.3 months (4.4-14.3). The median PFS in the p53abn group (n=8) was 3.2 months (2.3-4.2); however, PFS did not reach the median (p = 0.001) in the MMRd/NSMP group (n=12). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and a response was observed in all cases, irrespective of the molecular subtype. No treatment-related deaths occurred. Conclusion: The IHC-based ProMisE molecular classification system provides useful information for patient selection for LEN/PEM therapy.