{"product_id":"angiogenesis-inhibitors-plus-parp-inhibitors-for-maintenance-treatment-of-advanced-ovarian-cancer-a-patient-guide-to-a-major-meta-analysis","title":"Angiogenesis Inhibitors Plus PARP Inhibitors for Maintenance Treatment of Advanced Ovarian Cancer: A Patient Guide to a Major Meta-Analysis","description":"\u003cp\u003eThis meta-analysis combined data from nine studies and 1,074 patients with advanced ovarian cancer to evaluate maintenance treatment with angiogenesis inhibitors (AIs) plus PARP inhibitors (PARPi). The overall objective response rate (ORR) was 57%, and results were strongest in patients with platinum-sensitive recurrent ovarian cancer (ORR 70%, median progression-free survival 12.4 months, median overall survival 40.8 months). The rate of severe treatment-related side effects (Grade ≥3) was 22%, which the authors judged acceptable. The authors concluded that the combination is a feasible and safe first-line maintenance option, especially for platinum-sensitive disease.\u003c\/p\u003e\n\n\u003ch1\u003eAngiogenesis Inhibitors Plus PARP Inhibitors for Maintenance Treatment of Advanced Ovarian Cancer: A Patient Guide to a Major Meta-Analysis\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow the Research Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#results\"\u003eKey Findings: What the Numbers Show\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#discussion\"\u003eClinical Implications: What This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What the Study Could Not Prove\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations and Actionable Advice\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a meta-analysis of nine studies and 1,074 patients, combining angiogenesis inhibitors with PARP inhibitors for advanced ovarian cancer produced an overall response rate of 57%.\u003c\/li\u003e\n\u003cli\u003ePatients with platinum-sensitive recurrent ovarian cancer had the most favorable results: 70% response rate, median progression-free survival 12.4 months, and median overall survival 40.8 months.\u003c\/li\u003e\n\u003cli\u003eAbout 22% of patients experienced severe (Grade 3 or higher) treatment-related side effects; the most common were stomach pain, high blood pressure, and anemia.\u003c\/li\u003e\n\u003cli\u003eThe authors concluded the combination is feasible and safe as a first-line maintenance option, especially for platinum-sensitive disease, but noted the small sample and variation among studies.\u003c\/li\u003e\n\u003cli\u003ePatients are advised to discuss combination maintenance therapy, platinum sensitivity status, and clinical trial options with their oncology team.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eOvarian cancer ranks as the fifth most common cause of cancer death in women. Fewer than 50% of women with ovarian cancer survive five years after diagnosis. Most patients are treated first with cytoreductive surgery. Cytoreductive surgery is surgery to remove as much tumor as possible. Most patients also receive systemic chemotherapy. Systemic chemotherapy uses drugs that travel through the bloodstream to reach cancer cells throughout the body.\u003c\/p\u003e\n\n\u003cp\u003eMost patients respond completely to this initial treatment. However, most patients eventually experience a recurrence (the cancer comes back). The average survival after recurrence is less than 12 months. This poor outlook has driven researchers to look for better maintenance treatments — therapies given after the initial response to delay or prevent recurrence.\u003c\/p\u003e\n\n\u003cp\u003eTargeted therapy is now widely recognized as a successful treatment for many cancers. Two important classes of targeted drugs are anti-angiogenesis inhibitors (AIs) and poly ADP ribose polymerase inhibitors (PARPi).\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAngiogenesis inhibitors\u003c\/strong\u003e work by disrupting the formation of new blood vessels that tumor cells need to grow and spread. \u003cstrong\u003ePARP inhibitors\u003c\/strong\u003e block a DNA repair enzyme called poly ADP ribose polymerase, which cancer cells rely on to fix damaged DNA.\u003c\/p\u003e\n\n\u003cp\u003eThree PARP inhibitors — olaparib, niraparib, and rucaparib — have been approved by the US Food and Drug Administration (FDA) for maintenance therapy in ovarian cancer. In Europe, olaparib, niraparib, and rucaparib have been approved for maintenance treatment and third-line treatment, respectively. These drugs are approved in platinum-sensitive, relapsed ovarian cancer with BRCA1\/2 mutations. They are approved after a complete or partial response to platinum-based chemotherapy.\u003c\/p\u003e\n\n\u003cp\u003ePrevious trials have shown promising results for combining these drug classes. In the PAOLA-1 study, the median progression-free survival (PFS — the time before the cancer worsens) was 22.1 months for olaparib plus bevacizumab compared with 16.6 months for placebo plus bevacizumab. In another trial, combining niraparib with bevacizumab produced an 18-month PFS rate of 62% in the intention-to-treat population, with a median PFS of 19.6 months.\u003c\/p\u003e\n\n\u003cp\u003eBecause of these notable clinical advantages, the number of clinical trials investigating AIs combined with PARPi for maintenance treatment of advanced ovarian cancer has increased. The authors of this study performed the first systematic review and meta-analysis to thoroughly evaluate the effectiveness and safety of this combination.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow the Research Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003eThis meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards. A meta-analysis combines results from multiple studies to produce a single, more reliable estimate of treatment effect. The study was registered at PROSPERO with registration number CRD42024543590.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers searched four major databases: PubMed, Embase, Web of Science, and the Cochrane Library. They looked for articles published from the inception of each database until January 15, 2024. The search used terms including \"ovarian cancer,\" \"PARP inhibitor,\" \"angiogenesis inhibitors,\" and \"randomized controlled trial.\" The researchers also manually examined the bibliographies of identified papers. The researchers also manually examined relevant reviews and meta-analyses. This was done to find any additional research that met the inclusion criteria.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eInclusion criteria\u003c\/strong\u003e for the analysis were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003ePatients diagnosed with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer\u003c\/li\u003e\n  \u003cli\u003eAt least one cohort of patients received maintenance AIs combined with PARPi\u003c\/li\u003e\n  \u003cli\u003eAt least one of the following outcomes was reported: objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or Grade ≥3 adverse events (serious side effects)\u003c\/li\u003e\n  \u003cli\u003eStudy types: randomized controlled trials or single-arm trials\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003eExclusion criteria\u003c\/strong\u003e were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eOther article types such as case reports, publications, letters, reviews, meta-analyses, editorials, pharmacological intervention studies, animal studies, and protocols\u003c\/li\u003e\n  \u003cli\u003eStudies involving other diseases\u003c\/li\u003e\n  \u003cli\u003eIrrelevant studies\u003c\/li\u003e\n  \u003cli\u003eStudies from which data could not be extracted\u003c\/li\u003e\n  \u003cli\u003eStudies with duplicate patient cohorts\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eTwo independent reviewers selected the studies. They removed duplicate entries using EndNote software (Version 21; Clarivate Analytics). The reviewers assessed titles and abstracts for relevance and categorized each study as included or excluded. When the two reviewers disagreed, a third reviewer acted as a mediator to reach a consensus.\u003c\/p\u003e\n\n\u003cp\u003eTwo autonomous reviewers extracted data from each study. The collected data included the first author's name, year of publication, study area, trial ID, study design, and sample size. The collected data also included intervention, age of participants, trial phase, study period, and median follow-up duration. The collected data also included ORR, Grade ≥3 adverse events, and Kaplan-Meier curves for OS and PFS. Kaplan-Meier curves are graphs that show how many patients remain alive or free of cancer progression over time.\u003c\/p\u003e\n\n\u003cp\u003eTwo unbiased reviewers evaluated the quality of the included studies. They used the modified Jadad scale and the Cochrane Collaboration risk of bias assessment tool (ROB) for randomized controlled trials. They used the methodological index for non-randomized studies (MINORS) for single-arm trials.\u003c\/p\u003e\n\n\u003cp\u003eAll analyses were performed using Stata 16.0 software. The researchers used the \"meta\" package and IPDformKM package. GetData Graph Digitizer software extracted data from articles containing Kaplan-Meier curves. Individual patient data were reconstructed using the IPDformKM package and the established method by Guyot et al.\u003c\/p\u003e\n\n\u003cp\u003eContinuous variables were compared using the weighted mean difference (WMD) with a 95% confidence interval (CI). A 95% CI means that if the study were repeated many times, the true value would fall within this range in 95% of those repetitions. Relative ratio (RR) with 95% CI compared binary variables. Medians and interquartile ranges of continuous data were converted to means and standard deviations.\u003c\/p\u003e\n\n\u003cp\u003eStatistical heterogeneity between included studies was calculated using the Cochrane Q test and the I² index. An I² greater than 50% indicated significant heterogeneity (meaning the studies differed substantially from each other). When there was high heterogeneity among studies, the random effects model was adopted; otherwise, the fixed effects model was used. A P value less than 0.05 was considered statistically significant. Finally, a sensitivity analysis was performed to determine the impact of individual studies on the aggregated results and to test the reliability of the results.\u003c\/p\u003e\n\n\u003ch2 id=\"results\"\u003eKey Findings: What the Numbers Show\u003c\/h2\u003e\n\n\u003cp\u003eThe initial search discovered a total of 1,224 studies. After eliminating unnecessary research, 755 papers were kept. After assessing titles and abstracts, 24 publications were deemed inappropriate and excluded. Following a thorough examination of the full text, nine studies were included in the meta-analysis.\u003c\/p\u003e\n\n\u003cp\u003eThe nine included studies comprised six randomized controlled trials and three single-arm trials, with a total of 1,074 patients diagnosed with advanced ovarian cancer. Six trials used olaparib, and three used niraparib. All trials were considered to be of high quality based on the modified Jadad scale and MINORS assessment.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers conducted subgroup analyses to address differences in patient inclusion criteria across trials. The three subgroups were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003ePlatinum-resistant recurrent ovarian cancer (cancer that has come back within six months of platinum-based chemotherapy)\u003c\/li\u003e\n  \u003cli\u003ePlatinum-sensitive recurrent ovarian cancer (cancer that has come back more than six months after platinum-based chemotherapy)\u003c\/li\u003e\n  \u003cli\u003eNewly diagnosed advanced ovarian cancer\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eObjective Response Rate (ORR)\u003c\/h3\u003e\n\n\u003cp\u003eThe overall pooled ORR for patients with advanced ovarian cancer who received AIs combined with PARPi was \u003cstrong\u003e57%\u003c\/strong\u003e (95% CI, 35% to 77%). The ORR measures the percentage of patients whose tumors shrank or disappeared after treatment.\u003c\/p\u003e\n\n\u003cp\u003eIn subgroup analysis, the ORR results were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-resistant recurrent ovarian cancer:\u003c\/strong\u003e 30% (95% CI, 12% to 52%)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-sensitive recurrent ovarian cancer:\u003c\/strong\u003e 70% (95% CI, 61% to 78%)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNewly diagnosed advanced ovarian cancer:\u003c\/strong\u003e 59% (95% CI, 55% to 63%)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThis finding suggests that resistance to AIs combined with PARPi may be linked to resistance to platinum-based chemotherapy.\u003c\/p\u003e\n\n\u003ch3\u003eProgression-Free Survival (PFS)\u003c\/h3\u003e\n\n\u003cp\u003eAfter reconstructing the patient cohort, the researchers evaluated PFS using Kaplan-Meier curves. The median PFS results were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-resistant recurrent ovarian cancer:\u003c\/strong\u003e 5.8 months (95% CI, 5.3 to 7.1 months)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-sensitive recurrent ovarian cancer:\u003c\/strong\u003e 12.4 months (95% CI, 10.6 to 13.2 months)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNewly diagnosed advanced ovarian cancer:\u003c\/strong\u003e 22.4 months (95% CI, 21.5 to 24.2 months)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eOverall Survival (OS)\u003c\/h3\u003e\n\n\u003cp\u003eThe researchers also evaluated OS using Kaplan-Meier curves. The median OS results were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-resistant recurrent ovarian cancer:\u003c\/strong\u003e 15.5 months (95% CI, 12.3 to 24.8 months)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-sensitive recurrent ovarian cancer:\u003c\/strong\u003e 40.8 months (95% CI, 33.4 to 45.2 months)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNewly diagnosed advanced ovarian cancer:\u003c\/strong\u003e 56.3 months (95% CI, 49.0 to 62.0 months)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe outcomes of OS and PFS demonstrated that the combination of AIs and PARPi yielded more favorable oncological prognosis for patients with platinum-sensitive recurrent ovarian cancer. This was compared with patients with platinum-resistant recurrent ovarian cancer.\u003c\/p\u003e\n\n\u003ch3\u003eGrade ≥3 Treatment-Related Adverse Events (TRAEs)\u003c\/h3\u003e\n\n\u003cp\u003eThe Grade ≥3 TRAEs rate was found to be \u003cstrong\u003e0.22\u003c\/strong\u003e (95% CI, 0.13 to 0.33) among patients with advanced ovarian cancer who received AIs combined with PARPi. This means that approximately 22% of patients experienced a severe treatment-related side effect.\u003c\/p\u003e\n\n\u003cp\u003eIn subgroup analysis, the Grade ≥3 TRAEs rate was:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-resistant recurrent ovarian cancer:\u003c\/strong\u003e 0.21 (95% CI, 0.18 to 0.24)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlatinum-sensitive recurrent ovarian cancer:\u003c\/strong\u003e 0.13 (95% CI, 0.10 to 0.17)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNewly diagnosed advanced ovarian cancer:\u003c\/strong\u003e 0.42 (95% CI, 0.39 to 0.45)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe most often seen Grade ≥3 TRAEs of the combined medication were stomach pain, hypertension (high blood pressure), and anemia (low red blood cell count). These side effects align with the adverse reactions typically associated with monotherapy (using one drug alone).\u003c\/p\u003e\n\n\u003ch2 id=\"discussion\"\u003eClinical Implications: What This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThe findings from this study revealed that patients with advanced ovarian cancer who were administered AIs plus PARPi had an ORR of 57%, indicating favorable antitumor efficacy of the combined treatment. The notable advantage of AIs and PARPi for patients with advanced ovarian cancer was evident in terms of PFS and OS. This confirms that the combination therapy should be recommended as the first-line therapy for patients with advanced ovarian cancer.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers explained why this combination may work better than either drug alone. AIs play a crucial role in malignancy treatment by disrupting the formation of new blood vessels that tumor cells require for growth and metastasis. Specifically:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCediranib\u003c\/strong\u003e acts as a potent inhibitor of vascular endothelial growth factor receptors (VEGFRs), effectively blocking endothelial cell proliferation and survival.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBevacizumab\u003c\/strong\u003e is a monoclonal antibody that directly neutralizes VEGF, preventing its interaction with receptors on the endothelial cell surface.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAnlotinib\u003c\/strong\u003e is a multi-targeted kinase inhibitor that not only inhibits VEGFR but also acts on other pathways like PDGFR and FGFR, reinforcing its anti-angiogenic effects.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAIs or PARPi exhibit substantial efficacy as monotherapy for recurrent ovarian cancer. However, prolonged usage of a single agent can lead to the development of drug resistance. Previous research suggests that AIs plus PARP inhibition may boost anticancer efficacy.\u003c\/p\u003e\n\n\u003cp\u003eStudies have demonstrated that antiangiogenic drugs have multiple effects on homologous recombination deficiency (HRD — a condition where cancer cells cannot repair certain types of DNA damage). These effects include reducing angiogenesis, creating hypoxia (low oxygen) in the tumor microenvironment, and downregulating BRCA1\/2 and RAD51, two of the most important components in HRD.\u003c\/p\u003e\n\n\u003cp\u003eBevacizumab is linked to an elevated occurrence of hypoxia-induced HRD deficiency in tumor cells. Cells exhibiting heightened HRD may display more vulnerability to PARPi. AIs have the ability to bind with PARPi, resulting in mutually reinforcing anticancer effects.\u003c\/p\u003e\n\n\u003cp\u003eHomologous recombination repair deficiency is a frequent feature of high-grade serous ovarian, fallopian tube, and peritoneal carcinoma (HGSC). This deficiency is associated with sensitivity to PARP inhibitors.\u003c\/p\u003e\n\n\u003cp\u003eAdditionally, PARPi may possibly have a role in the process of angiogenesis. Although vascular growth factor is present, the deletion of PARP1 in mice resulted in a decrease in angiogenesis. This indicates a possible antiangiogenic action of PARPi. The upregulation of PARPi in human epithelial ovarian cancer tissues is correlated with parameters such as a high pathological grade and the spread of cancer cells to the lymph nodes. This indicates that PARPi may play a role in the advancement of ovarian cancer. However, PARP-1 is overexpressed and may also stimulate angiogenesis in epithelial ovarian cancer cells by increasing the expression of VEGFA.\u003c\/p\u003e\n\n\u003cp\u003ePreclinical studies have demonstrated that the combination of PARPi and AIs exhibits a synergistic effect (the combination works better than the sum of their individual effects). This combination effectively inhibits the invasion of ovarian cancer cells and the creation of microvascular endothelial tubes. PARPi and AIs modify the genetic makeup of tumor cells, both directly and indirectly, in order to enhance the effectiveness of therapy.\u003c\/p\u003e\n\n\u003cp\u003eFurthermore, PARP inhibitors could be used in combination with other targeted therapies, including immunotherapies such as PD-1\/PD-L1 inhibitors, to enhance the ability to attack tumor cells. However, the precise mechanisms underpinning these combinations remain poorly understood and may vary depending on the specific anti-angiogenic drugs involved. Additional research is required to clarify the precise mechanism through which this combination produces its anticancer effects.\u003c\/p\u003e\n\n\u003cp\u003eWith respect to safety, the rate of Grade ≥3 TRAEs was determined to be 22%. This indicates that the occurrence of negative effects from the combination therapy was deemed acceptable. In clinical trials examining the use of AIs alone, the most often seen Grade ≥3 TRAEs were high blood pressure, blood clotting events, low levels of neutrophils (a type of white blood cell), and bleeding outside of the central nervous system. In clinical trials examining the use of PARPi alone, the most often seen Grade ≥3 TRAEs were anemia, thrombocytopenia (low platelet count), neutropenia, fatigue, and nausea.\u003c\/p\u003e\n\n\u003cp\u003eThe present study had numerous strengths. First, this study was an updated systematic review and meta-analysis to evaluate the effectiveness and safety of PARPi in conjunction with AIs for advanced ovarian cancer. Although Wei Y et al. conducted a meta-analysis about effectiveness and safety of PARPi plus AIs for advanced ovarian cancer, there were serious drawbacks in the previous meta-analysis. Four of the seven studies included in the previous meta-analysis contained duplicate patients from the PAOLA-1 trials, which led to a significant bias.\u003c\/p\u003e\n\n\u003cp\u003eThis study performed an expanded search strategy with additional search terms to ensure a comprehensive literature review. Nine trials studying PARPi plus AIs for advanced ovarian cancer were included, which resulted in more accurate results. Additionally, the IPDformKM package was utilized to reconstruct Kaplan-Meier curves for PFS and OS, providing a clear and comprehensible representation of oncological outcomes. Furthermore, a subgroup analysis was performed to resolve discrepancies in the patient inclusion criteria observed in different studies. This study provides empirical support to inform the practical application of AIs in combination with PARPi for the management of patients with advanced ovarian cancer.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What the Study Could Not Prove\u003c\/h2\u003e\n\n\u003cp\u003eThe study has specific limitations that patients and clinicians should consider.\u003c\/p\u003e\n\n\u003cp\u003eFirst, the sample size was quite small. The analysis included only nine trials, involving a total of 1,074 individuals diagnosed with advanced ovarian cancer who were treated with AIs plus PARPi.\u003c\/p\u003e\n\n\u003cp\u003eSecond, the inclusion of single-arm clinical trials resulted in indirect comparisons between different treatment protocols. The researchers failed to perform the meta-analysis of hazard ratio (HR) value estimates from Kaplan-Meier curves regarding PFS or OS. One reason was that several single-arm trials did not provide HR values since there was no control group. Another reason was that the regimens of the control groups in different randomized controlled trials were not the same.\u003c\/p\u003e\n\n\u003cp\u003eAs an alternative method, Kaplan-Meier curves for OS and PFS were reconstructed using the IPDformKM package, which presented an intuitive representation for oncological outcomes. This method has been reported previously by Guyot et al.\u003c\/p\u003e\n\n\u003cp\u003eThird, the nine studies exhibited significant variation in terms of research technique, patient characteristics, and treatment regimens. Therefore, the explanation of the findings requires a certain level of caution.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations and Actionable Advice\u003c\/h2\u003e\n\n\u003cp\u003eBased on the findings of this meta-analysis, the combination of PARPi and AIs is both viable and safe for treating advanced ovarian cancer. The findings validate the recommendation of combination therapy as the primary treatment option for individuals diagnosed with advanced ovarian cancer.\u003c\/p\u003e\n\n\u003cp\u003eThe findings show improved survival and progression-free survival, as well as a reduction in treatment-related adverse events, in platinum-resistant recurrent ovarian cancer and in newly diagnosed advanced ovarian cancer.\u003c\/p\u003e\n\n\u003cp\u003eFor patients and their families, these findings suggest the following:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss combination maintenance therapy with your oncology team.\u003c\/strong\u003e The combination of an angiogenesis inhibitor plus a PARP inhibitor may be recommended as first-line maintenance treatment for advanced ovarian cancer.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eUnderstand your platinum sensitivity status.\u003c\/strong\u003e Patients with platinum-sensitive recurrent ovarian cancer had the most favorable outcomes. These outcomes were ORR 70%, median PFS 12.4 months, and median OS 40.8 months. This was compared with patients with platinum-resistant disease. Patients with platinum-resistant disease had ORR 30%, median PFS 5.8 months, and median OS 15.5 months.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBe aware of potential side effects.\u003c\/strong\u003e Approximately 22% of patients experienced Grade ≥3 treatment-related adverse events. The most common severe side effects were stomach pain, high blood pressure, and anemia.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about clinical trial options.\u003c\/strong\u003e The researchers note that additional research is needed to clarify the precise mechanisms through which this combination produces its anticancer effects.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRecognize the limitations.\u003c\/strong\u003e The analysis included a relatively small number of patients (1,074) across nine studies. The authors advise caution in interpreting the findings because of variation among the studies.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eThe authors conclude that the combination of PARPi and AIs is both viable and safe for treating advanced ovarian cancer. The findings validate the recommendation of combination therapy as the primary treatment option for individuals diagnosed with advanced ovarian cancer.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is maintenance treatment for advanced ovarian cancer?\u003c\/h3\u003e\n\u003cp\u003eMaintenance treatment is therapy given after the initial response to surgery and chemotherapy, with the goal of delaying or preventing the cancer from returning. This meta-analysis looked at combining two types of targeted drugs — angiogenesis inhibitors, which disrupt the blood vessels tumors need, and PARP inhibitors, which block a DNA repair enzyme cancer cells rely on — as maintenance for advanced ovarian cancer.\u003c\/p\u003e\n\u003ch3\u003eHow well did the combination of angiogenesis inhibitors and PARP inhibitors work overall?\u003c\/h3\u003e\n\u003cp\u003eAcross nine studies and 1,074 patients with advanced ovarian cancer, the overall objective response rate was 57%, meaning that percentage of patients had tumors shrink or disappear. Results varied by subgroup: the response rate was 70% in platinum-sensitive recurrent disease, 59% in newly diagnosed disease, and 30% in platinum-resistant recurrent disease.\u003c\/p\u003e\n\u003ch3\u003eWhat does platinum-sensitive mean, and why does it matter for this treatment?\u003c\/h3\u003e\n\u003cp\u003ePlatinum-sensitive means the cancer came back more than six months after platinum-based chemotherapy. In this analysis, patients with platinum-sensitive recurrent ovarian cancer had the most favorable outcomes: a 70% response rate, median progression-free survival of 12.4 months, and median overall survival of 40.8 months. Patients with platinum-resistant disease, whose cancer returned within six months, had lower results.\u003c\/p\u003e\n\u003ch3\u003eWhat side effects did patients experience with this combination?\u003c\/h3\u003e\n\u003cp\u003eAbout 22% of patients in the analysis experienced a severe treatment-related side effect, known as Grade 3 or higher. The most common were stomach pain, high blood pressure, and anemia (low red blood cell count). These side effects are similar to those seen when either drug class is used alone. The authors judged the rate acceptable.\u003c\/p\u003e\n\u003ch3\u003eHow long did patients live without the cancer getting worse?\u003c\/h3\u003e\n\u003cp\u003eMedian progression-free survival — the time before the cancer worsened — was 12.4 months for platinum-sensitive recurrent ovarian cancer, 22.4 months for newly diagnosed advanced ovarian cancer, and 5.8 months for platinum-resistant recurrent ovarian cancer. Median overall survival was 40.8 months, 56.3 months, and 15.5 months respectively for those groups.\u003c\/p\u003e\n\u003ch3\u003eCan I ask my oncology team about this combination therapy?\u003c\/h3\u003e\n\u003cp\u003eThe authors concluded the combination is feasible and safe as a first-line maintenance option, especially for platinum-sensitive disease, and suggest discussing combination maintenance therapy with your oncology team. You can also ask about your platinum sensitivity status and whether clinical trials are available, since more research is needed to clarify how the combination works.\u003c\/p\u003e\n\u003ch3\u003eWhat are the limitations of this analysis?\u003c\/h3\u003e\n\u003cp\u003eThe analysis included only nine trials and 1,074 patients, which is a relatively small sample. It also included single-arm trials, leading to indirect comparisons, and the studies varied in design, patient characteristics, and treatment regimens. The authors advise caution in interpreting the findings for these reasons.\u003c\/p\u003e\n\u003ch3\u003eWhen should a patient with advanced ovarian cancer considering angiogenesis inhibitors plus PARP inhibitors as maintenance treatment seek a second opinion?\u003c\/h3\u003e\n\u003cp\u003eA second opinion can help when the recommended maintenance plan does not match your platinum sensitivity status. In platinum-sensitive recurrent ovarian cancer, the objective response rate was 70%, median progression-free survival 12.4 months, and median overall survival 40.8 months; in platinum-resistant disease, these were 30%, 5.8 months, and 15.5 months. Approximately 22% of patients had Grade ≥3 side effects, most often stomach pain, high blood pressure, and anemia. An independent review can confirm whether the combination fits your situation. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Efficacy and safety of angiogenesis inhibitors combined with poly ADP ribose polymerase inhibitors in the maintenance treatment of advanced ovarian cancer: a meta-analysis.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Renming Huang, Feng Ji, Leyi Huang, Yueying Qin, Zhiyu Liang, Miaoyan Huang, Chunyan Li, and Jian Ban\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAffiliation:\u003c\/strong\u003e The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, China\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e Frontiers in Oncology, Volume 14, Article 1477105\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication date:\u003c\/strong\u003e November 18, 2024\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e 10.3389\/fonc.2024.1477105\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eSystematic review registration:\u003c\/strong\u003e PROSPERO identifier CRD42024543590\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e This work was supported by the Key Laboratory Construction Project of Guangxi Health Commission (ZPZH2020007), the Scientific Research Foundation of Guangxi University of Science and Technology (20Z13), the Scientific Research Foundation of Guangxi Health Commission (Z-B20220927), and the Scientific Research Foundation of Guangxi Health Commission (Z-B20220930).\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47807328026780,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/products\/angiogenesis-inhibitors-plus-parp-inhibitors-for-maintenance-treatment-of-advanced-ovarian-cancer-a-patient-guide-to-a-major-meta-analysis","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}