Rutie Yin

A multicenter, prospective, non-interventional drug intensive monitoring study of olaparib in a large real-world Chinese patient cohort with ovarian cancer (DIM-OC)

Abstract 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.

Analysis of the global burden of ovarian cancer in adolescents

Ovarian cancer is the most prevalent gynecologic malignancy in adolescents, predominantly characterized by non-epithelial cancer. We aim to analyze the epidemiological characteristics of ovarian cancer in various regions and countries within this specific population. This is a cross-sectional study using data from the Global Burden of Disease 2021 study, which included adolescents with ovarian cancer aged 15 to 24 years in 204 countries and territories from 1990 to 2021. We retrieved data on incidence, mortality, and disability-adjusted life years, and calculated estimated annual percentage changes to assess the temporal trends. In addition, we explored the relationship between the disease burden and the Socio-demographic Index and performed decomposition analysis. Globally, in 2021, the incidence, mortality, and disability-adjusted life years for ovarian cancer among adolescents were reported as 11,087 (95% CI 8893-12,899), 1573 (95% CI 1249-1832), and 115,075 (95% CI 91,622-134,050), respectively, with all corresponding age-standardized rates showing increasing trends from 1990 to 2021. Among the 5 Socio-demographic Index regions, the middle Socio-demographic Index region exhibited the highest age-standardized incidence rate (2.27, 95% CI 1.75-2.66), while the region with the highest age-standardized mortality rate and the most significant increase in disease burden was the low-middle region. Furthermore, out of 21 geographical regions, Southeast Asia reported the highest age-standardized incidence rate (4.48, 95% CI 3.00-6.12), while Central Latin America had the highest age-standardized mortality rate (0.42, 95% CI 0.36-0.49). Andean Latin America had the greatest increase in disease burden, while Australasia had the greatest decrease. The disease burden of ovarian cancer among adolescents continues to rise globally, particularly in regions and countries with moderate to low economic development. Enhancing the equitable allocation of health care resources to facilitate early diagnosis and treatment is essential for future treatment and research strategies.

Application of anti-angiogenic drugs in ovarian cancer from the perspective of bibliometrics

Bibliometric and visual analysis of immune checkpoint inhibitors for ovarian cancer

Real-world study of elderly patients with epithelial ovarian cancer: The identifying and unmet needs

The role of innate immunity triggered by HPV infection in promoting cervical lesions

Innate immunity is the immune system that organisms possess from birth. It is primarily responsible for the rapid, nonspecific recognition of pathogens when they invade, activating the host's immune response to eliminate. Cervical cancer is one of the most well-known tumors caused by human papillomavirus (HPV) infection. As the first line of defense against pathogens, innate immunity plays a crucial role in the response to HPV invasion, and there has been significant research in this area in recent years. The findings suggest that innate immune responses not only contribute to the clearance of HPV but may also facilitate the spread of the virus and the carcinogenic transformation of cervical epithelial cells. In this review, we comprehensively examine the activation of innate immune responses during HPV infection, the mechanisms by which HPV evades these immune defenses, and the role of innate immunity in promoting cervical intraepithelial neoplasia. Additionally, we explore the characteristics of innate immune responses within the tumor microenvironment of cervical cancer. Furthermore, we summarize recent advances in understanding the various mechanisms by which innate immune responses can be activated, with a focus on potential therapeutic implications. By reviewing the latest research, this article aims to provide valuable insights and stimulate further investigation into the role of innate immunity in HPV-associated cervical lesions, potentially leading to more effective strategies for prevention and treatment in the future.

An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline BRCA1/2 Mutation and Platinum-sensitive Recurrent Ovarian Cancer

Abstract Purpose: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer. Patients and Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1. Results: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5–18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6–78.2] and 70.8% (95% CI, 61.5–79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3–13.9) and 10.3 months (95% CI, 9.2–12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2–96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred. Conclusions: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial

PURPOSE This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA)

Abstract Purpose: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer. Patients and Methods: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan–Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453). Results: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs. Conclusions: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201

Pamiparib Monotherapy for Patients with Germline BRCA1/2 -Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study

Abstract Purpose: Phase I results of this phase I/II study showed that pamiparib 60 mg twice a day had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer. Patients and Methods: This open-label phase II study was conducted in China and enrolled adult (≥18 years) patients with platinum-sensitive ovarian cancer (PSOC; disease progression occurring ≥6 months after last platinum treatment) or platinum-resistant ovarian cancer (PROC; disease progression occurring <6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCAmut) and had previously received ≥2 lines of therapy. Pamiparib 60 mg orally twice a day was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1. Results: In the total patient population (N = 113; PSOC, n = 90; PROC, n = 23), median age was 54 years (range, 34–79) and 25.6% of patients received ≥4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2–21.5). Eighty-two patients with PSOC and 19 patients with PROC were evaluable for efficacy. In patients with PSOC, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% [95% confidence interval (CI), 53.3–74.9]. In patients with PROC, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6–56.6). Frequently reported grade ≥3 adverse events were hematologic toxicities, including anemia and decreased neutrophil count. Conclusions: Pamiparib 60 mg twice a day showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCAmut, and had a manageable safety profile.

Dose Prediction Models Based on Geometric and Plan Optimization Parameter for Adjuvant Radiotherapy Planning Design in Cervical Cancer Radiotherapy

The prediction of an additional space for the dose sparing of organs at risk (OAR) in radiotherapy is still difficult. In this pursuit, the present study was envisaged to find out the factors affecting the bladder and rectum dosimetry of cervical cancer. Additionally, the relationship between the dose-volume histogram (DVH) parameters and the geometry and plan dose-volume optimization parameters of the bladder/rectum was established to develop the dose prediction models and guide the planning design for lower OARs dose coverage directly. Thirty volume modulated radiation therapy (VMAT) plans from cervical cancer patients were randomly chosen to build the dose prediction models. The target dose coverage was evaluated. Dose prediction models were established by univariate and multiple linear regression among the dosimetric parameters of the bladder/rectum, the geometry parameters (planning target volume (PTV), volume of bladder/rectum, overlap volume of bladder/rectum (OV), and overlapped volume as a percentage of bladder/rectum volume (OP)), and corresponding plan dose-volume optimization parameters of the nonoverlapping structures (the structure of bladder/rectum outside the PTV (NOS)). Finally, the accuracy of the prediction models was evaluated by tracking d = (predicted dose-actual dose)/actual in additional ten VMAT plans. V30, V35, and V40 of the bladder and rectum were found to be multiple linearly correlated with the relevant OP and corresponding dose-volume optimization parameters of NOS (regression R2 > 0.99, P < 0.001 ). The variations of these models were less than 0.5% for bladder and rectum. Percentage of bladder and rectum within the PTV and the dose-volume optimization parameters of NOS could be used to predict the dose quantitatively. The parameters of NOS as a limited condition could be used in the plan optimization instead of limiting the dose and volume of the entire OAR traditionally, which made the plan optimization more unified and convenient and strengthened the plan quality and consistency.

Global research trends and frontiers in regulatory T cells within ovarian cancer: A bibliometric and visual analysis

First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial

First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer. ClinicalTrials.gov Identifier: NCT03635489.

A Trial of Maintenance Treatment With Fluzoparib Versus Placebo in Relapsed Ovarian Cancer Patients

To evaluate the efficacy, safety tolerability of maintenance therapy with Fluzoparib(A PARP inhibitor) versus placebo in Chinese patients with recurrent ovarian cancer who achieved a complete response (CR) or partial response (PR) after platinum-based chemotherapy

Olaparib Tablets Maintenance Monotherapy Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

This is a prospective, open-label, single arm, multi-centre interventional study to assess the clinical efficacy and safety of olaparib maintenance monotherapy and will be conducted in patients with platinum sensitive relapsed (PSR) high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy