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Background/Objectives: Platinum-resistant ovarian cancer (PROC) is a major therapeutic challenge, as it responds poorly to standard platinum-based treatment, has limited treatment options, and offers a generally unfavorable prognosis. Chemotherapeutic agents like pegylated liposomal doxorubicin (PLD), topotecan (TOPO), and gemcitabine (GEM) are used for this setting, but with varying efficacy and toxicity profiles, leading to an increasing need to understand the optimal balance between treatment effectiveness and tolerability for improving patient outcomes. This study evaluates the efficacy and side effects of PLD, TOPO, and GEM, focusing on progression-free survival (PFS), overall survival (OS), and safety profiles. Methods: We conducted a retrospective observational study that included 856 PROC patients treated with PLD (n = 383), TOPO (n = 352), or GEM (n = 121) at the OncoHelp Oncology Center from January 2018 to December 2023. Inclusion criteria encompass diagnosis, prior platinum therapy, and Eastern Cooperative Oncology Group (ECOG) status (0–2). Treatment protocols followed standard dosing, with adjustments for toxicity. Primary endpoints included PFS and OS, with safety assessed by incidence of grade 3 and 4 toxicities per CTCAE v5.0. Kaplan–Meier analysis and Cox regression were used to compare survival, and statistical significance was set at p < 0.05. Results: TOPO showed higher toxicity than PLD and GEM, including liver damage, hematological and non-hematological side effects, while PLD induced more skin toxicity. In terms of survival, minor differences were seen between the three chemotherapeutic agents, with a slight advantage for PLD for better disease control. Conclusions: Given the comparable results in OS across the regimens, treatment decisions should be based on other factors such as patient tolerance and quality of life. [ABSTRACT FROM AUTHOR]

Background This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. Methods Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval. Results Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P  < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed. Conclusion PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962. [ABSTRACT FROM AUTHOR]

Hao Su,1,&ast; Xiao Shang,1,&ast; Hongruo Liu,2 Yutong Wang,1 Yang Yu,3 Yanhua Xu,4 Kui Jiang,2,&ast; Fengzhi Feng1,&ast; 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Obstetrics and Gynecology, Xing’an League People’s Hospital, Xing’an League, Inner Mongolia, People’s Republic of China; 4Department of Obstetrics and Gynecology, Jinan Maternity and Child Health Care Hospital, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengzhi Feng, Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, People’s Republic of China, Email fengfz1969@sina.com Kui Jiang, Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116023, People’s Republic of China, Email jk0411@163.comPurpose: Therapeutic options for patients with platinum-resistant ovarian cancer (PROC) remain a major unmet need. PROC patients with multiple recurrences are unable to continue highly toxic treatment after prior multiple lines of systemic therapy. Chemotherapy-free option lenvatinib plus anti-programmed cell death protein-1 (PD-1) combination therapy has shown promising results in several malignancies including ovarian cancer, but the toxicity of a high starting dose of lenvatinib is also notable and needs to be improved. Our previous pilot study indicated that a reduced starting dose of lenvatinib may maintain comparable anti-tumor activity with favorable safety in heavily pre-treated ovarian cancer. This study is designed to further validate the efficacy and safety of the combination therapy of low-dose lenvatinib and PD-1 inhibitor toripalimab in patients with recurrent PROC.Study Design and Methods: The study is designed as a multicenter, open-label, single-arm, prospective phase II study. Patients with recurrent epithelial ovarian cancer who have disease progression either during or within 6 months after completion of platinum-based therapy will be included. A total of 69 participants will receive low-dose lenvatinib (8 mg or 12 mg, daily, orally, based on patient’s body weight) and toripalimab (240 mg, every 21 days, intravenously). Treatment will continue until the development of unacceptable toxicity or disease progression. The primary endpoint is the progression-free survival. The secondary endpoints include objective response rate, duration of response, disease control rate, overall survival, toxicity and patients’ quality of life. Exploratory objectives aim to identify biomarkers and molecular signatures for predicting response or prognosis.Keywords: ovarian cancer, platinum-resistant, immune checkpoint inhibitor, lenvatinib, dose adjustment

Background: With the emergence of new anti-angiogenic treatments and the ongoing updates to clinical guidelines, the effectiveness and safety of these agents in treating platinum-sensitive/resistant ovarian cancer (OC) are yet to be fully determined. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of anti-angiogenic drugs combined with chemotherapy (CT) for platinum-sensitive OC (PSOC) or platinum-resistant OC (PROC). Methods: A comprehensive literature search was conducted across several databases, including PubMed, Web of Science, Embase, and the Cochrane Library, encompassing all pertinent randomized controlled trials (RCTs) up to 31 May 2024. The primary outcomes for the meta-analysis were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR), adverse events (AEs) of any grade, and grade ≥3 AEs were considered secondary endpoints. Data synthesis involved the computation of hazard ratio (HR), relative risk (RR), along with their 95% confidence interval (CI) and prediction interval (PI). Trial sequential analysis was carried out using STATA 12.0, R software 4.3.1, and TSA v0.9.5.10 Beta software. Results: This meta-analysis encompassed 15 RCTs. The overall analysis revealed that compared to CT alone (or plus placebo), anti-angiogenic drugs combined with CT significantly improved PFS (HR [95% CI] = 0.573 [0.518–0.633], 95% PI: 0.383-0.876) and ORR (RR [95% CI] = 1.362 [1.260–1.472], 95% PI: 0.824–2.251), but also increased the incidence of grade ≥3 AEs (RR [95% CI] = 1.115 [1.070–1.162], 95% PI: 0.870–1.422) in PSOC patients. For PROC patients, this combination therapy notably improved PFS (HR [95% CI] = 0.542 [0.475–0.619], 95% PI: 0.322–0.930), OS (HR [95% CI] = 0.752 [0.646–0.875], 95% PI: 0.554-0.997), and ORR (RR [95% CI] = 2.141 [1.702–2.694], 95% PI: 0.839–5.307), whilst simultaneously elevating the risk of grade ≥3 AEs (RR [95% CI] = 1.487 [1.216–1.819], 95% PI: 0.755–2.828). Conclusion: Our research verified the advantages of combining anti-angiogenic agents with CT in enhancing PFS and ORR for patients with PSOC, and also confirmed improvements in PFS, OS, and ORR for those with PROC. It is crucial for medical practitioners to remain alert to the potential occurrence of AEs when implementing this combined therapeutic approach in a clinical milieu. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024552010. [ABSTRACT FROM AUTHOR]

Introduction: Genomic characterization of serous ovarian carcinoma (SOC), which includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), remains necessary to improve efficacy of platinum-based chemotherapy. The aim of this study was to investigate the genomic variations in these SOC groups, also in relation to chemoresponse. Methods: Forty-five samples of SOC were retrospectively analyzed by next-generation sequencing on DNA/RNA extracts from formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained at diagnosis. HGSCs were classified as platinum-resistant and platinum-sensitive. Results: In the LGSC group, 44% of the carcinomas had mutually exclusive variants in the RAS/RAF pathway, while additional likely oncogenic variants in the CDKN2A, SMARCA4, and YAP1 genes were observed in the remaining LGSCs. Tumor mutation burden (TMB) was significantly lower in the intrinsically chemoresistant LGSC group than in the HGSC group. In the HGSC cohort, TP53 variants were found in 90% and homologous recombination repair (HRR) pathway variants in 41% of the neoplasms. HGSCs of the chemoresistant group without classic mutations in the HRR pathway were characterized by additional variants in FGFR2 and with an FGFR3::TACC3 fusion. In addition, HGSCs showed MYC, CCNE1, and AKT2 gains that were almost exclusively observed in the chemosensitive HGSC group. Conclusion: These results suggest that very low TMB and MYC, CCNE1, and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy strategies. [ABSTRACT FROM AUTHOR]

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better tolerability profile without compromising efficacy.

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: Antibody-drug conjugates (ADCs) are a promising new treatment modality for patients with cancer. They have been approved by the US Food and Drug Administration for treating breast, gastric, cervical, and ovarian cancers (OC), as well as lymphoma and multiple myeloma. Recently, several ADCs have undergone clinical trials for OC, and their development is underway. Several unmet medical needs exist in OC, including treatment for patients with platinum recurrence. This new treatment modality may benefit these patients. ADCs, a new concept of agents, comprise an antibody, a linker, and a payload. If the target is expressed in tumors, the payload specifically reaches the tumor cells. This approach is particularly suitable for OC because of its heterogeneous nature. In this review, we describe the existing evidence for ADC use in OC treatment and discuss ongoing clinical trials. 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. [ABSTRACT FROM AUTHOR]

Background: Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy. Patients and Methods: In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival. Results: The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%). Conclusion: The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group. [ABSTRACT FROM AUTHOR]

BackgroundWith the emergence of new anti-angiogenic treatments and the ongoing updates to clinical guidelines, the effectiveness and safety of these agents in treating platinum-sensitive/resistant ovarian cancer (OC) are yet to be fully determined. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of anti-angiogenic drugs combined with chemotherapy (CT) for platinum-sensitive OC (PSOC) or platinum-resistant OC (PROC).MethodsA comprehensive literature search was conducted across several databases, including PubMed, Web of Science, Embase, and the Cochrane Library, encompassing all pertinent randomized controlled trials (RCTs) up to 31 May 2024. The primary outcomes for the meta-analysis were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR), adverse events (AEs) of any grade, and grade ≥3 AEs were considered secondary endpoints. Data synthesis involved the computation of hazard ratio (HR), relative risk (RR), along with their 95% confidence interval (CI) and prediction interval (PI). Trial sequential analysis was carried out using STATA 12.0, R software 4.3.1, and TSA v0.9.5.10 Beta software.ResultsThis meta-analysis encompassed 15 RCTs. The overall analysis revealed that compared to CT alone (or plus placebo), anti-angiogenic drugs combined with CT significantly improved PFS (HR [95% CI] = 0.573 [0.518–0.633], 95% PI: 0.383-0.876) and ORR (RR [95% CI] = 1.362 [1.260–1.472], 95% PI: 0.824–2.251), but also increased the incidence of grade ≥3 AEs (RR [95% CI] = 1.115 [1.070–1.162], 95% PI: 0.870–1.422) in PSOC patients. For PROC patients, this combination therapy notably improved PFS (HR [95% CI] = 0.542 [0.475–0.619], 95% PI: 0.322–0.930), OS (HR [95% CI] = 0.752 [0.646–0.875], 95% PI: 0.554-0.997), and ORR (RR [95% CI] = 2.141 [1.702–2.694], 95% PI: 0.839–5.307), whilst simultaneously elevating the risk of grade ≥3 AEs (RR [95% CI] = 1.487 [1.216–1.819], 95% PI: 0.755–2.828).ConclusionOur research verified the advantages of combining anti-angiogenic agents with CT in enhancing PFS and ORR for patients with PSOC, and also confirmed improvements in PFS, OS, and ORR for those with PROC. It is crucial for medical practitioners to remain alert to the potential occurrence of AEs when implementing this combined therapeutic approach in a clinical milieu.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024552010.

The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era. Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval. From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities. Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel. • We explored real-world outcomes with bevacizumab (bev)/chemotherapy for platinum-resistant ovarian cancer. • Median time on treatment (ToT) was 3 months and overall survival (OS) was 11 months. • ToT (6 vs 3 months; p < 0.0001) and OS (14 vs 9; p = 0.0089) were longer with bev/paclitaxel than bev/liposomal doxorubicin. • OS was not significantly different for patients treated pre- and post-bev approval (8 vs 9 months; HR 1.01; p = 0.937). • Post-approval OS increased for patients receiving bev/paclitaxel (6 vs 11 months). [ABSTRACT FROM AUTHOR]

Background/Aim: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinumresistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. Patients and Methods: We retrospectively divided patients with PRROC into two groups: bevacizumab plus chemotherapy (BEVCT group) and chemotherapy alone (CT group). Progressionfree survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. Results: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. Conclusion: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity. [ABSTRACT FROM AUTHOR]

Abstract Background Almost all patients with ovarian cancer will experience relapse and eventually develop platinum-resistant. The poor prognosis and limited treatment options have prompted the search for novel approaches in managing platinum-resistant ovarian cancer (PROC). Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of combination therapy with vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors for PROC. Methods A comprehensive search of online databases was conducted to identify randomized clinical trials published until December 31, 2022. Pooled hazard ratios (HR) was calculated for overall survival (OS) and progression-free survival (PFS), while pooled odds ratio (OR) was calculated for objective response rate (ORR) and treatment-related adverse events (TRAEs). Subgroup analysis was further performed to investigate the source of heterogeneity. Results In total, 1097 patients from eight randomized clinical trials were included in this meta-analysis. The pooled HRs of OS (HR = 0.72; 95% CI: 0.62–0.84, p

Background: Almost all patients with ovarian cancer will experience relapse and eventually develop platinum-resistant. The poor prognosis and limited treatment options have prompted the search for novel approaches in managing platinum-resistant ovarian cancer (PROC). Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of combination therapy with vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors for PROC. Methods: A comprehensive search of online databases was conducted to identify randomized clinical trials published until December 31, 2022. Pooled hazard ratios (HR) was calculated for overall survival (OS) and progression-free survival (PFS), while pooled odds ratio (OR) was calculated for objective response rate (ORR) and treatment-related adverse events (TRAEs). Subgroup analysis was further performed to investigate the source of heterogeneity. Results: In total, 1097 patients from eight randomized clinical trials were included in this meta-analysis. The pooled HRs of OS (HR = 0.72; 95% CI: 0.62–0.84, p < 0.0001) and PFS (HR = 0.52; 95% CI: 0.45–0.59, p < 0.0001) demonstrated a significant prolongation in the combination group compared to chemotherapy alone for PROC. In addition, combination therapy demonstrated a superior ORR compared to monotherapy (OR = 2.34; 95%CI: 1.27–4.32, p < 0.0001). Subgroup analysis indicated that the combination treatment of VEGF/VEGFR inhibitors and chemotherapy was significantly more effective than monochemotherapy in terms of OS (HR = 0.71; 95% CI: 0.61–0.84, p < 0.0001), PFS (HR = 0.49; 95% CI: 0.42–0.57, p < 0.0001), and ORR (OR = 2.97; 95% CI: 1.89–4.67, p < 0.0001). Although the combination therapy was associated with higher incidences of hypertension, mucositis, proteinuria, diarrhea, and hand-foot syndrome compared to monochemotherapy, these toxicities were manageable and well-tolerated. Conclusions: The meta-analysis demonstrated that combination therapy with VEGF/VEGFR inhibitors yielded better clinical outcomes for patients with PROC compared to monochemotherapy, especially when combined with chemotherapy. This analysis provides more treatment options for patients with PROC. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42023402050. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent ovarian cancer is one of the most challenging issues in medical oncology. Being the fifth in the cancer mortality list among women, ovarian cancer is the reason of more deaths than any other cancer of the female reproductive system. A meta-analysis was conducted to investigate the optimal treatment options for recurrent platinum-sensitive and platinum-resistant ovarian cancer. Methods: Data for writing this article was collected from the publications in English, Russian and Italian from 2002 to 2023. PubMed and Web of Science were searched for the relevant articles. Survival rates, particularly overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of the chemotherapy regimens were discussed. We analyzed the literature data comparing the effectiveness and safety of chemotherapy, antiangiogenic therapy, the use of poly-ADP ribose polymerase (PARP) inhibitors, and checkpoint inhibitors in the treatment of recurrent ovarian cancer. Results: An overview of the literature devoted to modern approaches to the systemic treatment of recurrent ovarian cancer is given in the article. General principles of classification and treatment of recurrent ovarian cancer are analyzed. The existing regimens of chemotherapy in combination with targeted therapy are given separately for various types of ovarian cancer relapses. Chemotherapy with doublet platinum compounds (carboplatin or cisplatin) continues to be the standard of care in platinum-sensitive relapsed ovarian cancer with or without targeted therapy. Treatment with poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, immunotherapy with checkpoint inhibitors, and antibody-drug conjugate for patients with folate receptor alpha-positive, can be considered in platinum-resistant epithelial ovarian cancer. Conclusion: In summary, we can conclude that despite the success of the primary treatment of ovarian cancer, the majority of patients with a widespread tumor process develop a relapse of the disease over the next two years, which is the cause of death of these patients. The development of effective treatment regimens for recurrent ovarian/fallopian tube/primary peritoneal cancer remains particularly acute and important in gynecological oncology and requires further study. [ABSTRACT FROM AUTHOR]

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6–20% and progression-free survival of ≈3–4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov) In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join. Significant unmet need in platinum-resistant #ovariancancer (PROC) treatment. ARTISTRY-7 (NCT05092360), a global #clinicaltrial, is evaluating efficacy & safety of investigational nemvaleukin + pembrolizumab vs chemotherapy in previously treated PROC. #immunotherapy #cytokine. [ABSTRACT FROM AUTHOR]

Background: In the last decades, growing attention has been focused on identifying effective therapeutic strategies in the orphan clinical setting of women with platinum-resistant ovarian cancer (PROC), generating thousands of original articles. However, the literature involving bibliometric analysis of PROC has not been published yet. Objective: This study hopes to gain a better understanding of the hot spots and trends in PROC by conducting a bibliometric analysis, as well as identify potential new research directions. Methods: We searched the Web of Science Core Collection (WOSCC) for PROCrelated articles published between 1990 and 2022. CiteSpace 6.1.R2 and VOS viewer 1.6.18.0 were primarily utilized to evaluate the contribution and cooccurrence relationships of various countries and regions, institutes, and journals and to identify research hotspots and promising future trends in this research field. Results: A total of 3,462 Web of Science publications were retrieved that were published in 671 academic journals by 1135 authors from 844 organizations in 75 countries and regions. The United States was the leading contributor in this field, and the University of Texas MD Anderson Cancer Center was the most productive institution. Gynecologic Oncology was the most productive journal, while the Journal of Clinical Oncology was the most cited and influential. Co-citation cluster labels revealed the characteristics of seven major clusters, including synthetic lethality, salvage treatment, human ovarian-carcinoma cell line, PARP inhibitor resistance, antitumor complexes, folate receptor, and targeting platinum-resistant disease. Keywords and references burst detection indicated that biomarkers, genetic and phenotypic changes, immunotherapy, and targeted therapy were the most recent and most significant aspects of PROC research. Conclusion: This study conducted a comprehensive review of PROC research using bibliometric and visual techniques. Understanding the immunological landscape of PROC and identifying the population that can benefit from immunotherapy, especially in combination with other therapeutic options (such as chemotherapy and targeted therapy), will continue to be the focal point of research. [ABSTRACT FROM AUTHOR]

Background/Aim: In patients with advanced platinum-resistant ovarian cancer we prospectively evaluated whether trabectedin could resensitize the tumor cells to platinum rechallenge. Patients and Methods: Upon progression to platinum-based chemotherapy, trabectedin was administered as a 3-hour infusion every three weeks and subsequently crossed over to carboplatin/carboplatin-based combinations. The primary endpoints comprised objective response rate (ORR) and time to progression after trabectedin (TTP Trab). Secondary endpoints included ORR following platinum post-trabectedin, the growth modulation index (GMI) assessed as the ratio of successive TTP to platinum, given after (TTP2) and before (TTP1) trabectedin, quality of life (QoL), and ancillary translational studies. Results: Ten patients with platinum-resistant ovarian cancer from a single institution were treated with trabectedin, one of whom achieved a partial response (PR) reaching the ORR of 10% and six had stable disease (SD) for a disease control rate (DCR) of 70%. After the treatment with platinum posttrabectedin, one patient achieved a PR and two had SD, attaining a rate of resensitization to platinum of 37.5%. The median TTP with trabectedin treatment was 15.0 weeks, while eight patients who received platinum post-trabectedin had the median TTP2 of 19.9 weeks. One patient reached the threshold of GMI >1 (12.5%) as indicator of clinical benefit. QoL of patients was not deteriorated with trabectedin. Predictive biomarkers of response to trabectedin and/or re-exposure to platinum could not be identified. Conclusion: Although trabectedin did not achieve a wide resensitization to platinum in this heavily pretreated platinum-resistant population, a significant number of patients attained disease control. [ABSTRACT FROM AUTHOR]

Abstract Background The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. Methods One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. Discussion The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. Trial registration ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.

Abstract Background Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer. Objective To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase. Results This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis. Discussion The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant’s progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021. Trial registration ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018

Introduction: The survival benefits of surgical cytoreduction in ovarian cancer are well‐established. However, the surgical outcome has never been assessed while controlling for the efficacy of chemotherapy. This leaves the possibility that cytoreduction may not be beneficial for patients whose cancer does not respond well to adjuvant treatment. We sought to answer whether surgical cytoreduction independently improves overall survival when controlling for chemotherapy outcome. Material and Methods: We performed a retrospective case–control study using our institution's ovarian cancer database to evaluate the effect of optimal cytoreduction on advanced stage, high‐grade serous ovarian cancer. Patients' characteristics were compared using both univariate and multivariate regression modeling to assess for independent predictors of overall survival. Results: A total of 470 patients were assessed for inclusion; 234 responders to chemotherapy and 98 nonresponders. Significant survival characteristics were identified and included in the multivariate analysis. Independent predictors of survival in the multivariate analysis were age, responder status, optimal cytoreduction, neoadjuvant chemotherapy, and number of chemotherapy cycles. Kaplan–Meier survival curves showed improved survival for both patients who responded to chemotherapy and for those undergoing optimal cytoreduction (p < 0.001). We also demonstrated improved survival for patients receiving optimal cytoreduction among both nonresponders and responders (p < 0.001). Conclusions: Our analysis shows that patients who undergo optimal cytoreduction have an overall survival benefit regardless of their response to chemotherapy. Therefore, cytoreduction should be considered in all patients, even in those with advanced disease, if an optimal result can be achieved. This study was underpowered to assess patients who received neoadjuvant chemotherapy as a separate subgroup, but the order of treatment was controlled for in the overall analysis. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The gold standard therapeutic approach is a combination of surgery plus chemotherapy. Unfortunately, 80% of patients with EOC suffer recurrence within 2-years and the overall response rate for platinum-resistant epithelial ovarian cancer to cytotoxic chemotherapy or poly-(adenosine diphosphate)-ribose polymerase (PARP) inhibitor is modest. New therapies are needed to improve overall survival. The role of immunotherapy has been established in endometrial and cervical cancers, however its effective use in EOC has been limited due to the intrinsic genomics and micro-immune environment associated with EOC. Studies evaluating immunotherapy, largely immune checkpoint inhibitors (ICI), have shown limited activity, yet some patients benefit greatly. Thus, significant efforts must be devoted to finding new strategies for the use of immunotherapy/immunomodulatory drugs (IMiDs). Immunotherapy has a well-tolerated safety profile; however, cost-effectiveness can be an obstacle. The aim of this article is to review the most recent research into the use of IMiDs in patients with platinum-resistant epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Qingli Cui, Yanhui Hu, Dongyang Ma, Huaimin Liu Department of Integrated Traditional and Western Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People’s Republic of ChinaCorrespondence: Huaimin LiuDepartment of Integrated Traditional and Western Medicine, The Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Zhengzhou 450008, People’s Republic of ChinaEmail huaiminliu@sina.comObjective: Anlotinib, an oral small-molecular tyrosine kinase inhibitor (TKI) on tumor angiogenesis and growth, has a wide spectrum of inhibitory effects on targets such as vascular endothelial growth factor receptors 2/3 (VEGFR2/3), etc. The efficacy and safety of anlotinib in the treatment of platinum-resistant or platinum-refractory ovarian cancer were evaluated.Patients and Methods: Patients with platinum-resistant or platinum-refractory ovarian cancer that treated with anlotinib in the Affiliated Cancer Hospital of Zhengzhou University from May 2018 to March 2020 were included. Medical records were reviewed in terms of objective response, survival outcomes, and safety.Results: A total of 38 patients were analyzed. The median progression-free survival and the median overall survival were 7.7 months (95% CI: 6.7– 8.7) and 16.5 months (95% CI: 13.3– 19.7), respectively. About 17 patients received anlotinib monotherapy, and the median progression-free survival was 7.7 months (95% CI: 6.3– 9.1). A total of 19 cases received anlotinib plus chemotherapy with a median progression-free survival of 8.0 months (95% CI: 4.8– 11.2). A total of 2 cases received anlotinib plus anti-PD-1 antibody pembrolizumab, and 1 case had partial response, the other progressive disease. The objective response rate was 42.1% while the disease control rate was 86.8%. A total of 5 patients experienced dose reduction from 12 mg to 10 mg because of adverse effects. The most common adverse effects were hypertension (31.6%), fatigue (28.9%), anorexia (26.3%) and hand-foot syndrome (23.7%). No treatment-related deaths were recorded.Conclusion: Anlotinib produced moderate improvements in progression-free survival and overall survival in patients with platinum-resistant or platinum-refractory ovarian cancer. It indicates that anlotinib maybe a new treatment option for patients with platinum-resistant or platinum-refractory ovarian cancer.Keywords: angiogenesis, anlotinib, ovarian cancer, platinum-resistant

Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence in situ hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background: The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer.Methods: One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up.Discussion: The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial.Trial Registration: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018. [ABSTRACT FROM AUTHOR]

Abstract Background This study aimed to evaluate the efficacy and safety of apatinib with a low dose of 250 mg/d in the treatment of platinum‐resistant or platinum‐refractory ovarian cancer patients. Methods Patients with platinum‐resistant or platinum‐refractory ovarian carcinoma treated with 250 mg/d apatinib in our institution from November 2016 to December 2017 were retrospectively reviewed. The tumor response and progression were evaluated according to the standard by incorporating the levels of CA125 and Response Evaluation Criteria in Solid Tumors 1.1. CTCAE 4.03 was used to evaluate adverse events (AEs). Results Fifty‐two eligible patients were enrolled in per‐protocol (PP) analysis and 65 patients (including 13 lost to follow‐up) were included in the intention‐to‐treat (ITT) analysis. In PP analysis, 18 patients (34.6%) had partial response (PR), 22 patients (42.3%) had stable disease (SD), and the disease control rate (DCR) was 61.5%. Median progression‐free survival (PFS) was 4.0 months (95% CI, 2.83‐5.17 m), and median overall survival (OS) was 25.33 months (95% CI, 17.74‐32.92 m). The objective response rate and DCR for patients in ITT analysis were 27.7% and 49.2%, respectively. The top three treatment‐related AEs were hypertension, hand‐foot syndrome, and leukopenia. Eight patients (15.4%) in PP population had grade 3 treatment‐related AEs. Previous chemotherapy lines, number of recurrences, and AEs did not affect the efficacy of apatinib. Age older than 60 was associated with higher rates of disease control and prolonged PFS (P

Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence in situ hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients.

Background: Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer.Objective: To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase.Results: This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis.Discussion: The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant's progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021.Trial Registration: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018. [ABSTRACT FROM AUTHOR]

Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8+ T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated. Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers. [ABSTRACT FROM AUTHOR]

Until to date, platinum derived drugs are still the backbone of treating ovarian cancer (OC). Most patients treated with platinum-based chemotherapy develop resistance during the course of their management. The treatment of platinum-resistant ovarian cancer (PROC) is challenging. Few therapeutic options are available for patients with this aggressive disease. Besides, there are liminal advances regarding new anticancer drugs as well as validated predictive biomarkers of clinical outcomes in this setting. The enrollment of PROC patients in interventional studies is limited as compared to newly launched clinical trials for platinum-sensitive OC. Enthusiastically, the emergence of antibody-drug conjugates (ADCs) has provided promising findings for further clinical development in PROC. ADCs have the advantage to selectively deliver cytotoxic drugs to cancer cells expressing several of antigens using specific monoclonal antibodies based on the concept of immune bioconjugation. This innovative class of therapeutics showed encouraging early signs of clinical efficacy in PROC particularly mirvetuximab soravtansine that has been successfully introduced into three randomized and controlled phase III studies. In this review, the evidence from clinical trials supporting the development of ADCs targeting folate receptor alpha, sodium-dependent phosphate transporter 2B, dipeptidase 3, mesothelin, mucin 16, and tissue factor using various cytotoxic payloads in PROC is reviewed. [ABSTRACT FROM AUTHOR]

Our objective was to assess safety and adverse events associated with intraperitoneal Olvi-Vec virotherapy in patients with platinum-resistant or refractory ovarian cancer (PRROC). Secondary objectives included objective response rate (ORR) per RECIST 1.1 and progression-free survival (PFS). Olvi-Vec is a modified vaccinia virus that causes oncolysis and immune activation. An open-label phase 1b trial using a 3 + 3 dose escalation was conducted. Intraperitoneal Olvi-Vec was given as monotherapy in two consecutive daily doses. Translational analyses included anti-virus antibody levels, viral shedding, circulating tumor cells (CTCs) and T cells. Twelve patients (median age: 69 years, range: 45–77) with median 5 prior therapies (range: 2–10) and 2 prior platinum lines (range: 1–5) were enrolled. There were three dose level cohorts: 3 × 109 (n = 6), 1 × 1010 (n = 5), and 2.5 × 1010 (n = 1) plaque forming units (PFU)/day on two consecutive days. Treatment-related adverse events (TRAEs) included G1/G2 nausea (n = 6), fever (n = 6), abdominal distention (n = 5), and abdominal pain (n = 4). There were no Grade 4 TRAEs, no dose relationship to TRAEs, and no deaths attributed to Olvi-Vec. The ORR was 9% (1/11). Stable disease (SD) was 64% (7/11), and SD ≥15 weeks was 46% (5/11). Median PFS was 15.7 weeks (95%CI: 5.7–34.5), including extended PFS in four patients (23.2, 34.5, 59.4+ and 70.8 weeks). Three patients had extended overall survival (deceased 33.6 months, and alive with disease at 54 and 59 months). CTCs diminished in 6/8 (75%) baseline-positive patients. Immune activation was demonstrated from virus-enhanced tumor infiltration of CD8+ T-cells and activation of tumor-specific T-cells in peripheral blood. Oncolytic viral therapy with intraperitoneal Olvi-Vec showed promising safety, clinical activities, and immune activation in patients with PRROC, warranting further clinical investigation. • Intraperitoneal Olvi-Vec was well tolerated in this phase 1 study of platinum-resistant/refractory ovarian cancer. • Nausea, fever, and abdominal distension were the most common treatment-related adverse events. • The ORR with monotherapy Olvi-Vec was 9%, stable disease ≥15 weeks was 46%, median PFS was 15.7 (95% CI: 5.7–34.5) weeks. • Three patients had extended overall survival (33.6 to 59+ months) following additional cytotoxic therapies. • Virus-induced tumor-specific T-cell activation in blood and CD8+ T-cell infiltration into tumor tissue were demonstrated. [ABSTRACT FROM AUTHOR]

MUC16 is overexpressed in the majority of human epithelial ovarian cancers (OC). DMUC4064A is a humanized anti-MUC16 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. This trial assessed the safety, tolerability, pharmacokinetics, and preliminary activity of DMUC4064A in patients with platinum-resistant OC. DMUC4064A was administered once every 3 weeks to patients in 1.0–5.6 mg/kg dose escalation cohorts, followed by cohort expansion at the recommended Phase II dose (RP2D). Sixty-five patients were enrolled and received a median of 5 cycles (range 1–20) of DMUC4064A. The maximum tolerated dose was not reached; 5.2 mg/kg was the RP2D based on the overall tolerability profile. The most common adverse events were fatigue, nausea, abdominal pain, constipation, blurred vision, diarrhea, and anemia. Sixteen patients (25%) experienced related grade ≥ 3 toxicities. Twenty-six patients (40%) experienced ocular toxicities. The exposure of acMMAE was dose proportional, with a half-life of ~6 days. Sixteen patients (25%) experienced confirmed objective partial response (PR or CR) starting at ≥3.2 mg/kg dose levels, while 23 (35%) patients had best responses of PR or CR. Overall, the clinical benefit rate was 42% (27 patients with a best response [confirmed and unconfirmed] of CR, or PR or SD lasting ≥6 months). Among the 54 patients with high MUC16 immunohistochemistry scores, the clinical benefit rate was 46% (25 patients). Median progression-free survival was 3.9 months overall. In this Phase I study, DMUC4064A demonstrated a tolerable safety profile along with encouraging efficacy in the indication of platinum-resistant OC. • Treatment of platinum-resistant ovarian cancer is associated with poor response rates. • Antibody-drug conjugates have a wider therapeutic index in comparison to small molecules. • DMUC4064A is an anti-MUC16 THIOMAB™-drug conjugate, synthesized to have a more homogenous payload than ADCs. • DMUC4064A had a tolerable safety profile, and preliminary activity in 25% of patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to present our own retrospective data about the effectiveness of Bevacizumab (BV) maintenance therapy on survival to achieve optimal treatment in recurrent ovarian cancer. Methods: The data of patients with recurrent ovarian, tubal, and primary peritoneal cancer presenting to our hospital between October 2008 and December 2019 were retrospectively gathered from the hospital's electronic archive system. The patients were grouped according to the platinum-free interval state. The patients were divided into two groups of BV maintenance and no BV maintenance and their progression-free and overall survival were calculated. Results: A total of 65 patients with recurrent epithelial ovarian cancer were included in the study. Among these, 35 had received bevacizumab therapy alone and 30 received bevacizumab maintenance therapy. According to the platinum-free interval, 37 of the patients had platinumsensitive recurrent epithelial ovarian cancer and the remaining 28 had platinum-resistant recurrent epithelial ovarian cancer. The median follow-up was 42 (min: 13-max: 135) months. The average age was 56.5 ± 9.1 in the no bevacizumab maintenance group and 57.5 ± 9.6 in the bevacizumab maintenance group (p: 0.812). Among the platinum-sensitive recurrent epithelial ovarian cancer patients, the median progression-free survival progression-free survival (PFS) was 8 months (95% Confidence Interval (CI); 5.7-10.2) in the no bevacizumab maintenance group and 22 months (95% CI; 18.9-24.1) (p: 0.001) in the bevacizumab maintenance group and for the bevacizumab maintenance patients Hazard Ratio (HR): 0.10 (95% CI; 0.03-0.27) (p: 0.001). While the median overall survival (OS) of platinum-sensitive recurrent epithelial ovarian cancer patients in the no bevacizumab maintenance group was 64 months (95% CI; 21.6-102.3), it was 86 months (95% CI; NA) (p: 0.155) in the group that received bevacizumab maintenance, and for patients who received bevacizumab maintenance therapy, HR: 0.55 (95% CI; 0.18-1.33) (p: 0.166). The median PFS for platinum-resistant recurrent epithelial ovarian cancer patients who received no bevacizumab maintenance was determined as 7 (95% CI; 4.8-9.1) and as 19 months (95% CI; 9.2-26.7) (p: 0.009) for patients who received bevacizumab maintenance therapy, and for patients who received BV maintenance therapy, HR: 0.17 (95% CI; 0.03-0.71) (p: 0.022). In terms of OS, the median OS of platinum-resistant recurrent epithelial ovarian cancer patients who received no bevacizumab maintenance was 34 (95% CI; 31.5-36) months, while it was 45 (95% CI; 42.5-47.4) months in patients who received bevacizumab maintenance (p: 0.231); the HR for death in patients receiving bevacizumab maintenance therapy: 0.50 (95% CI; 0.15-1.61) (p: 0.247). Discussion: While it was shown that bevacizumab maintenance therapy had a significant effect on progression-free survival in both platinum-sensitive and platinumresistant ovarian cancer, this effect could not be demonstrated for overall survival. Despite this, bevacizumab maintenance therapy can be delivered in recurrent ovarian cancer in addition to standard therapy. Further studies about its effect on overall survival are required. [ABSTRACT FROM AUTHOR]

The randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer. Patients were randomly assigned (1:1) to lurbinectedin 3.2 mg/m2 1-h i.v. infusion q3wk (experimental arm), versus PLD 50 mg/m2 1-h i.v. infusion q4wk or topotecan 1.50 mg/m2 30-min i.v. infusion Days 1–5 q3wk (control arm). Stratification factors were PS (0 vs. ≥1), prior PFI (1–3 months vs. >3 months), and prior chemotherapy lines (1–2 vs. 3). The primary endpoint was PFS by Independent Review Committee in all randomized patients. This study was registered with ClinicalTrials.gov , NCT02421588. 442 patients were randomized: 221 in lurbinectedin arm and 221 in control arm (127 PLD and 94 topotecan). With a median follow-up of 25.6 months, median PFS was 3.5 months (95% CI, 2.1–3.7) in the lurbinectedin arm and 3.6 months (95% CI, 2.7–3.8) in the control arm (stratified log-rank p = 0.6294; HR = 1.057). Grade ≥ 3 treatment-related adverse events (AEs) were most frequent in the control arm: 64.8% vs. 47.9% (p = 0.0005), mainly due to hematological toxicities. The most common grade ≥ 3 AEs were: fatigue (7.3% of patients) and nausea (5.9%) with lurbinectedin; mucosal inflammation (8.5%) and fatigue (8.0%) in the control arm. The primary endpoint of improvement in PFS was not met. Lurbinectedin showed similar antitumor efficacy and was better tolerated than current standard of care in patients with platinum-resistant ovarian cancer. • Progression-free survival and safety of lurbinectedin was evaluated in patients with platinum-resistant ovarian cancer. • Lurbinectedin did not show improvement in PFS compared to pegylated liposomal doxorubicin (PLD) or topotecan. • Lurbinectedin showed similar efficacy and was better tolerated than current standard-of-care. [ABSTRACT FROM AUTHOR]

Platinum-resistant, high-grade serous ovarian cancer (HGSOC) has limited treatment options. Preclinical data suggest that poly(ADP-ribose) polymerase inhibitors (PARPi) and ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) are synergistic. CAPRI (NCT03462342) is an investigator-initiated study of olaparib plus ceralasertib in recurrent HGSOC. Herein, we present results from the platinum-resistant cohort. A Simon 2-stage design was utilized. Platinum-resistant HGSOC patients received ceralasertib 160 mg orally daily, days 1–7 and olaparib 300 mg orally twice daily, days 1–28 of a 28-day cycle until toxicity or progression. Primary endpoints were toxicity and efficacy including objective response rate (ORR) by RECIST. Secondary endpoint was progression-free survival (PFS). The null hypothesis (≤5% ORR) would be rejected if there were ≥ 1 responses in 12 patients. Fourteen PARPi-naïve patients were evaluable for toxicity; 12 were evaluable for response. Three had BRCA1 mutations (1 germline, 2 somatic). Adverse events possibly related to treatment were primarily grade (G) 1/2. G3 toxicities included nausea (14.3%), fatigue (7.1%), anorexia (7.1%), and anemia (7.1%). No objective responses occurred. Best response was stable disease in 9 patients and progressive disease in three. Five patients had a ≥ 20% to <30% reduction in disease burden, including 3 with BRCA1 mutations. Three of 11 patients (27%; 2 with BRCA1 mutations) evaluable by Gynecologic Cancer Intergroup criteria had >50% CA-125 decline, including 2 with CA-125 normalization. Median PFS was 4.2 months overall (90% CI:3.5–8.2) and 8.2 months (3.6 months–not determined) for patients with BRCA1 mutations. Olaparib plus ceralasertib is well-tolerated. No objective responses occurred, though a signal of activity was seen particularly in disease associated with BRCA1. Further evaluation of this combination should include alternate dosing strategies in genomically-selected populations. • Combination olaparib and ceralasertib is tolerable at the current RP2D. • No RECIST radiological responses occurred and PFS was 4.2 months. • PFS was 8.2 months in 3 subjects with BRCA1 mutations. • CA-125 responses by GCIG criteria were seen in 3 of 11 evaluable subjects. • A signal of activity was seen in DNA repair deficient platinum resistant HGSOC. [ABSTRACT FROM AUTHOR]

Tivozanib is a potent selective pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer (OC). This open-label phase II study used a Simon's two-stage design. Eligible patients had recurrent, platinum-resistant OC and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily for 21 days in a 28-day cycle. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. Thirty-one patients were enrolled, and 30 were treated. The median age was 59.5 years, and median number of prior regimens was 4 (range 1–9). Twenty-four patients were evaluable for response, and four (16.7%) achieved a partial response (PR; ORR = 16.7%). An additional fourteen (58.3%) patients had stable disease (SD). The clinical benefit rate (PR + SD) was 75.0%, and the median duration of objective response was 5.7 months. For all patients on trial, the median PFS was 4.1 months (95% confidence interval (CI): 1.7–5.8) and OS 8.6 months (95% CI: 5.4–12.5). There were no treatment-related deaths. Serious adverse events occurred in 13.3% of patients and included small intestinal perforation or obstruction and stroke. Grade 3–4 adverse events occurred in 60% of patients, including hypertension (26.7%) and fatigue (10%). Tivozanib is effective in patients with recurrent OC, with moderate toxicity and no treatment-related deaths, supporting its further development. • Tivozanib is a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor. • Response rate to Tivozanib in platinum-resistant ovarian cancer is 16.7%; median progression-free survival is 4.1 months. • The most common adverse events were fatigue and hypertension. [ABSTRACT FROM AUTHOR]

Abstract Introduction Bevacizumab and gemcitabine are key drugs for treating recurrent epithelial ovarian cancer. However, information about the combination of bevacizumab and gemcitabine is insufficient. We conducted a phase II study to assess the feasibility, clinical activity, and toxicity of this combination chemotherapy. Methods This study included women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer who received one to three regimens of platinum-based chemotherapy between April 1, 2015 and December 31, 2018. The patients received bevacizumab 15 mg/kg intravenously on day 1 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the completion rate of three cycles of chemotherapy. This study was registered in the University Medical Information Network (UMIN) Clinical Trials Registry (UMIN000016619). Results Among the 19 patients, 18 (95%) received ≥3 and 9 (47%) received ≥6 cycles of the study therapy. The objective response rate was 42% (complete response of 16% and partial response of 26%), and the clinical control rate was 84%. Hematological toxicity included neutropenia grade 3/4 in 9 patients (47%), anemia grade 3/4 in 2 (11%), and thrombocytopenia grade 3/4 in 1 (5%). One patient (5%) had grade 3 hypertension, and 1 (5%) had grade 3 protein urea. Possibly related grade 3 pulmonary toxicity was observed in 1 patient. Three patients needed dose reduction of gemcitabine to 800 mg/m2 due to treatment delay by 15 to 21 days on day1. There was no treatment delay more than 14 days on day 8. The median progression-free survival duration was 5.1 months and median overall survival duration was 21.3 months. Conclusion The combination chemotherapy with gemcitabine and bevacizumab was feasible, effective and safe. This combination chemotherapy may be explored in a further randomized trial.

Jindi Zhang,1,2,* Anyang Li,2,* Qi Jiang,2 Feiyun Zheng,2 Haiyan Zhu1,2 1Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Pudong, Shanghai 200126, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyan ZhuDepartment of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 2699 Gaoke West Road, Pudong, Shanghai 200126, People’s Republic of ChinaTel +86 137 5846 5255Email zhuhaiyandoc@sina.comObjective: To evaluate real-world use and outcomes of apatinib treatment in platinum-resistant recurrent epithelial ovarian cancer.Methods: This is an observational study. Patients with platinum-resistant recurrent epithelial ovarian cancer initiating apatinib treatment from January 2016 to December 2018 were included. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, disease control rate, and toxicity.Results: A total of 28 platinum-resistant epithelial ovarian cancer patients were enrolled in this study. Thirteen cases received apatinib as maintenance therapy following chemotherapy with a median progression-free survival of 6.0 months and a medium overall survival of 11.0 months. Four patients received apatinib as palliative following chemotherapy with 2 cases in progressive disease and 2 cases in stable disease. Eleven cases received apatinib alone as salvage therapy with a disease control rate of 81.8% and a median progression-free survival of 3.0 months. The most common adverse effects were hand-foot syndrome (53.57%), secondary hypertension (46.43%) and fatigue (14.29%). Five patients discontinued treatment due to grade 3 toxicities and 4 patients required dose reduction because of adverse effects.Conclusion: Apatinib produced moderate improvements in progression-free survival in patients with platinum-resistant epithelial ovarian cancer both as maintenance therapy following chemotherapy and as single-agent salvage therapy. Our study suggests that apatinib may be effective for women with platinum-resistant recurrent epithelial ovarian cancer.Keywords: epidermal growth factor receptor, apatinib, ovarian cancer, platinum-resistant, maintenance therapy

ObjectiveTo evaluate the value of serum Human epididymis protein 4 (HE4) for predicting the resistance of ovarian cancer (OS) to platinum chemotherapy.MethodWe searched the MEDLINE (PubMed), EMBASE, Cochrane Central, Web of Science, SCOPUS, and CNKI databases and screened all studies evaluating serum HE4 for predicting OC resistance to treatment with platinum. Two researchers independently evaluated the quality of all eligible original studies using QUADAS-2. RevMan 5.4 was used to compile the quality evaluation form. We also performed a meta-analysis with STATA15.1, and Deek’s funnel plots were used to detect any publication bias.ResultsEight studies were included in the final meta-analysis. Our results showed that the sensitivity and specificity of preoperative serum HE4 in predicting the resistance of OC to platinum chemotherapy was 80% and 67%, respectively. The diagnostic odds ratio was 8, and the AUC was 0.78 (95% CI: 0.75-0.82), whereas the pooled sensitivity and specificity of serum HE4 after the third-cycle of chemotherapies for predicting chemoresistance in OC was 86% and 85%, respectively, with a diagnostic odds ratio of 33 and AUC = 0.92 (95% CI: 0.89 – 0.94).ConclusionHE4 may be an effective predictor of platinum-based chemotherapeutic resistance of OC. Serum HE4 levels after the third chemotherapy cycle may be indicative for clinical practice. Further research is needed to validate the significance of HE4 in the long-term management of OC.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021220099).

Introduction: Gemcitabine is a nucleoside analog and pyrimidine antimetabolite that inhibits RNA synthesis, currently approved for use to treat a variety of cancers, among which ovarian cancers. Gemcitabine is considered relatively safe and it is generally well tolerated, with rarely reported cardiac side effects. Case report: We report a case of gemcitabine induced dilated cardiomyopathy in a 41-year-old woman receiving gemcitabine as second line treatment for platinum-resistant ovarian cancer without pre-existing hypertension or significant cardiac history. Management and Outcome: The patient presented with clinical symptoms and laboratory and imaging results suggestive of congestive cardiac failure, with a left ventricular ejection fraction of 15%. Gemcitabine administration was stopped and Furosemide with ACE-inhibitors and Beta-blocker agents were initiated. At that point the clinical situation improved: symptoms and findings disappeared with gemcitabine cessation. Discussion: Our case demonstrated for the first time objective evidence for dilated cardiomyopathy induced by gemcitabine in a young patient with platinum-resistant ovarian cancer without pre-existing significant cardiac history. Although rare, gemcitabine-induced cardiotoxicity should be promptly recognized in order to take appropriate measures to manage it. [ABSTRACT FROM AUTHOR]

Objective: To explore the short-term efficacy and adverse reactions of bevacizumab combined with doxorubicin liposomes in the treatment of patients with platinum-resistant recurrent epithelial ovarian cancer, as well as the survival of patients. Methods: A total of 76 patients with platinum-resistant recurrent epithelial ovarian cancer who were admitted to the 901 Hospital of the People's Liberation Army (PLA) Joint Logistic Support Force from January 2018 to December 2019 were enrolled in this study. The patients were divided into a control group and an observation group with 38 cases in each by random number grouping method. The control group was given doxorubicin liposome single-agent chemotherapy for 4 cycles, while the observation group was given bevacizumab combined with doxorubicin liposome chemotherapy for 4 cycles. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed, and the changes in serum tumor markers HE4 (human epididymis protein 4) and CA125 (carbohydrate antigen 125) were detected. In addition, the patients were followed up for overall survival (OS) and disease progressionfree survival (PFS). Results: The objective response rate (ORR) and disease control rate (DCR) of the control group were significantly lower than those of the observation group (ORR: 40.54% vs 69.44%; DCR: 67.57% vs 88.89%; all P<0.05). After treatment, the serum HE4 and CA125 levels of the observation group were (142.67±46.81) pmol/L and (31.79±11.65) U/L respectively, which were significantly lower than (219.33±75.67) pmol/L and (57.05±17.85) U/L of the control group (all P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, allergic reactions, thromboembolism, and bleeding between the two groups (all P>0.05); the incidence of hypertension in the observation group was significantly higher than that in the control group (P<0.05), but it was controllable and tolerable. The median OS and median PFS of the patients in observation group were 17.2 months and 10.9 months respectively, which were significantly longer than the 14.1 months and 7.8 months of the control group (all P<0.05). Conclusion: For patients with platinum-resistant recurrent epithelial ovarian cancer, bevacizumab combined with doxorubicin liposomes has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the value of serum Human epididymis protein 4 (HE4) for predicting the resistance of ovarian cancer (OS) to platinum chemotherapy. Method: We searched the MEDLINE (PubMed), EMBASE, Cochrane Central, Web of Science, SCOPUS, and CNKI databases and screened all studies evaluating serum HE4 for predicting OC resistance to treatment with platinum. Two researchers independently evaluated the quality of all eligible original studies using QUADAS-2. RevMan 5.4 was used to compile the quality evaluation form. We also performed a meta-analysis with STATA15.1, and Deek's funnel plots were used to detect any publication bias. Results: Eight studies were included in the final meta-analysis. Our results showed that the sensitivity and specificity of preoperative serum HE4 in predicting the resistance of OC to platinum chemotherapy was 80% and 67%, respectively. The diagnostic odds ratio was 8, and the AUC was 0.78 (95% CI: 0.75-0.82), whereas the pooled sensitivity and specificity of serum HE4 after the third-cycle of chemotherapies for predicting chemoresistance in OC was 86% and 85%, respectively, with a diagnostic odds ratio of 33 and AUC = 0.92 (95% CI: 0.89 – 0.94). Conclusion: HE4 may be an effective predictor of platinum-based chemotherapeutic resistance of OC. Serum HE4 levels after the third chemotherapy cycle may be indicative for clinical practice. Further research is needed to validate the significance of HE4 in the long-term management of OC. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ , PROSPERO (CRD42021220099). [ABSTRACT FROM AUTHOR]

Background: Treatment options are limited, and the prognosis is poor for patients with platinum-resistant recurrent metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). This study evaluated the efficacy and safety of a paclitaxel and ifosfamide (TI) regimen in patients with R/M HNSCC whose disease had progressed following platinum-based therapy., Patients and Methods: In this retrospective study, we included 53 patients with R/M HNSCC who underwent at least one cycle of TI-based therapy, post platinum failure, between February 2020 and August 2023. Some patients received the TI regimen in combination with immunotherapy and/or cetuximab. Key metrics assessed included the objective response rate (ORR), disease control rate, and progression-free as well as overall survival., Results: The study observed an ORR of 15.8% and a disease control rate of 36.8%. The median progression-free survival for the entire cohort was 3.3 months, and the median overall survival was 9.6 months. Notably, the combination of TI with immunotherapy yielded a higher ORR of 30.8%, compared to 14.3% with TI alone. The most prevalent grade 1-2 adverse events were anemia (81%), weight loss (68%) and hypernatremia (55%)., Conclusion: The TI-based regimen demonstrated favorable efficacy and safety profile in treating R/M HNSCC. Enhanced outcomes may be attainable when combining it with immunotherapy. This study suggests that TI-based therapy could serve as a potential salvage option for this specific patient group., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

IntroductionJUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma (KRAS) mutation.MethodsJUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety.ResultsBetween December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p = .77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p

Abstract Background Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. Methods We evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009–2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/−resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry). Results En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p

Introduction: JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma (KRAS) mutation. Methods: JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety. Results: Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p =.77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p <.000001). ORR was 8.9% and 2.7% (p =.010), and the disease control rate was 54.4% and 31.7% (p <.001) with abemaciclib and erlotinib, respectively. Safety results reflected the known safety profiles of abemaciclib and erlotinib. Conclusions: In this study, the primary endpoint of OS was not met; PFS and ORR were improved with manageable toxicity in the abemaciclib arm. The increases in response rates and PFS support further investigation of abemaciclib in other NSCLC subpopulations or in combination with other agents. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02152631 [ABSTRACT FROM AUTHOR]