Huaying Wang

Jing CY, et al. J Gynecol Oncol. 2025 Dec;37:e38. https://doi.org/10.3802/jgo.2026.37.e38

Background: Ovarian cancer (OC) is a highly lethal gynecological cancer. Olaparib maintenance therapy was effective and well-tolerated in pivotal RCTs. However, nationwide real-world safety information is limited in China. This multicenter, prospective, observational drug intensive monitoring study monitored the safety of olaparib in a largest-to-date, real-world Chinese OC cohort. Methods: Eligible OC patients had received ≥ 1 dose of olaparib. Follow-up extended up to 30 days post-olaparib discontinuation or maximally for six months post-enrolment. Primary and secondary endpoints were adverse events (AEs) in all OC patients and in special populations (hepatically/renally impaired before olaparib treatment; aged > 65 years), respectively. Results: By Jun 30, 2023, 799 patients from 33 sites were enrolled. By data cut-off (Dec 29, 2023), 796 patients treated with olaparib were analyzed. The median age was 55 years (range, 25–85). Of 796 patients, 490 (61.6%) were newly diagnosed and 306 (38.4%) had platinum-sensitive relapsed OC. AEs occurred in 343 (43.1%) patients, and 257 (32.3%) had treatment-related AEs. Anemia (19.2%) was the most common AE. Sixty-eight (8.5%) patients experienced grade ≥ 3 AEs, and 3 had AEs of special interest (AESIs; 0.4%; 1 myelodysplastic syndrome, 1 breast cancer, 1 pneumonitis). 45.2% (19/42) patients with hepatic impairment at baseline, 38.5% (5/13) with renal impairment at baseline and 38.6% (49/127) aged > 65 years experienced any AEs, respectively. No AESIs were reported in these subgroups. Conclusions: In this largest-to-date, first prospectively enrolled, real-world Chinese OC cohort, olaparib demonstrated a well-tolerated and manageable safety profile (including in special populations) with appropriate management, regardless of treatment lines. No new safety signals were identified.

The combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer. This single-arm Simon’s two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle. Between January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred. Camrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors. This trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.

Objective This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. Methods In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1–14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. Results 33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5–17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand–foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4–5 events or deaths were observed. Conclusion Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

Original Article Efficacy and safety of apatinib in patients with recurrent uterine malignancy: a prospective, single-center, single-arm, phase 2 study Yulan Ren, Tingting Wang, Xi Cheng, Guihao Ke, Yan Huang, Huijuan Yang, Xiao Huang, Wenjuan Tian, Huaying Wang

Shi T, et al. J Gynecol Oncol. 2022 Jun;33:e63. https://doi.org/10.3802/jgo.2022.33.e63

Epithelial ovarian carcinoma (EOC) is one of the most common gynecologic malignancies with a high mortality rate. Serum biomarkers and imaging approaches are insufficient in identifying EOC patients at an early stage. This study is to set up a combination of proteins from serum small extracellular vesicles (sEVs) for the diagnosis of early-stage EOC and to determine its performance. A biomarker for early-stage ovarian cancer (BESOC) cohort was used as a Chinese multi-center population-based biomarker study and registered as a Chinese Clinical Trial ChiCTR2000040136. The sEV protein levels of CA125, HE4, and C5a were measured in 299 subjects. Logistic regression was exploited to calculate the odds ratio and to create the sEV protein model for the predicted probability and subsequently receiver-operating characteristic (ROC) analysis. The combined sEV marker panel of CA125, HE4, and C5a as a sEV model obtained an area under curve (AUC) of 0.912, which was greater than the serum model (0.809), by ROC analysis to identify EOC patients from the whole cohort. With the cutoff of 0.370, the sensitivity and specificity of the sEV model were 0.80 and 0.89, which were much better performance than the serum markers (sensitivity: 0.55~0.66; specificity: 0.59~0.68) and the risk of ovarian malignancy algorithm (ROMA) index approved by the U.S. Food and Drug Administration (sensitivity: 0.65; specificity: 0.61), to identify EOC patients from patients with benign ovarian diseases or other controls. The sEV levels of CA125 significantly differed among early-stage and late-stage EOC (p < 0.001). Moreover, the AUC of ROC to identify early-stage EOC patients was 0.888. Further investigation revealed that the sEV levels of these 3 proteins significantly decreased after cytoreductive surgery (CA125, p = 0.008; HE4, p = 0.025; C5a, p = 0.044). In summary, our study showed that CA125, HE4, and C5a levels in serum sEVs can identify EOC patients at the early stage, elucidating the possibility of using a sEV model for the diagnosis of early-stage EOC.

Guan J, et al. J Gynecol Oncol. 2021 May;32(4):e60. https://doi.org/10.3802/jgo.2021.32.e60

Background: Epigenetic regulation by promoter methylation-mediated silencing of cancer-related microRNAs plays vital roles in tumorigenesis. MiR-192-5p promotes tumor progression in various human cancers with conflicting biological effects. However, its expression levels and biological functions in endometrial carcinoma (EC) have not been reported.

Purpose This study aimed to evaluate the risk factors of recurrence and invasive disease in patients with extramammary Paget’s disease of the vulva (EPDV). Methods We performed a retrospective analysis of patients who were initially diagnosed with EPDV in Fudan University Shanghai Cancer Center between May 2006 and March 2019. Results Thirty-eight patients were initially diagnosed with EPDV in our institution. Among them, 29 had intraepithelial EPDV, 8 had intraepithelial EPDV with stromal invasion, and 1 had an underlying vulvar adenocarcinoma. In total, 8 (21%) patients had 12 recurrences. Of these eight patients, four had one recurrence, while other four had two recurrences. Intraepidermal EPDV recurred nine times, while intraepidermal EPDV with invasive disease recurred thrice. The first and second recurrence intervals were 62.1 (9–146) months and 22 (15–28) months, respectively. The rate of invasive disease was 23.7% (9/38) for primary EPDV and 25% (3/12) for recurrent ones. We determined that the presence of invasive disease was associated with a history of more than 10 years (p = 0.02) and inversely correlated with positive margins (p = 0.037), However, invasive disease had no statistical relations with age (p = 0.438), recurrence (p = 0.642), and lesion diameter (p = 0.08). Conclusions EPDV with a history of more than 10 years was associated with invasive disease. Close and long-term follow-up are recommended to identify those who require further treatment.