Retrospective analysis of ovarian cancer patients treated with PARP inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17555-e17555
Author(s):  
Connie Liang ◽  
Ashley Leung ◽  
Chung-Shien Lee ◽  
Jennifer Hernandez ◽  
Kit Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Retrospective Study ◽  
Adverse Events ◽  
Parp Inhibitor ◽  
Time Frame ◽  
Parp Inhibitors ◽  
Primary Objective ◽  
Hematologic Toxicity ◽  
Single Institution ◽  
Cancer Data

e17555 Background: Over the last few years, targeted therapy has become the mainstay maintenance treatment of patients with ovarian cancer including patients with BRCA1 or BRCA2 mutations. Poly ADP ribose polymerase (PARP) inhibitors are effective in the treatment of patients who are in complete or partial remission. PARP inhibitors are known to cause hematological adverse events (AEs), but have not been compared directly to each other. Methods: We conducted a single institution, IRB approved, retrospective study on patients who were treated with PARP inhibitors from December 2016 to October 2020. Patients were stratified according to which PARP inhibitor they received. Our primary objective was to assess the incidence of hematological and non-hematological adverse events associated with the use of PARP inhibitor therapy used in patients with ovarian cancer. Data from absolute neutrophil count, hemoglobin and platelet count during the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Results: A total of 126 patients received a PARP inhibitor during the study time frame. 34 were excluded and 92 patients were included for analysis. Median age of patients were 64.3 (range, 33.8 to 92.3) years, 66 (71.7%) white, and 84 (91.3%) had an ECOG PS of 0/1. Thirty-one (33.7%) of patients received niraparib and 61 (66.3%) of patients received olaparib. Patients in the niraparib group experienced more hematologic AEs, with 11 (35.5%) (95% CI 19.2-54.6), 20 (64.5%) (95% CI 45.4-80.8), and 18 (58.1%) (95% CI 39.1-75.5) experiencing neutropenia, anemia, thrombocytopenia, respectively. Eight (13.1%) (95% CI 5.8-24.2), 24 (39.3%) (95% CI 27.1-52.7), 16 (26.2%) (95% CI 15.8-39.1) patients in the olaparib group experienced neutropenia, anemia, thrombocytopenia, respectively. Conclusions: This single institution retrospective study outlines the hematological toxicities observed between two PARP inhibitors. Although there are four PARP inhibitors approved by FDA, our data compared only two of the four (as they were the most commonly prescribed PARP inhibitors in our institution). Our results suggested that niraparib tended to be associated with a higher risk for hematologic toxicities than olaparib. Our data showed anemia as the most common hematologic toxicity which was consistent with what has been widely documented in the literature.

scholarly journals Sedation Protocol During Bevacizumab Intravitreal Injection in Preterm Infants With Retinopathy of Prematurity

2018 ◽  
Vol 23 (1) ◽  
pp. 34-40
Author(s):  
Jamie L. Miller ◽  
Peter N. Johnson ◽  
Kari Harkey ◽  
R. Michael Siatkowski
Keyword(s):  
Retrospective Study ◽  
Data Collection ◽  
Adverse Events ◽  
Retinopathy Of Prematurity ◽  
Intravitreal Bevacizumab ◽  
Primary Objective ◽  
Future Studies ◽  
Sedation Protocol ◽  
Number Of Patients ◽  
Sedation And Analgesia

OBJECTIVES This study describes outcomes of intravenous (IV) analgesics and sedatives for bedside intravitreal bevacizumab injections for retinopathy of prematurity. METHODS This retrospective study included infants receiving intravitreal bevacizumab injections between January 2012 and May 2016. Infants were excluded if bevacizumab was administered under general anesthesia or for incomplete records. Data collection included demographics, sedation and analgesia regimen, and cardiopulmonary adverse events (AEs). The primary objective was to identify the median doses of the IV analgesics and sedatives. The secondary objectives included the number of patients with cardiopulmonary AEs and those with procedure success, defined as procedure completion without interruption and absence of interventions. RESULTS Fifteen infants were included. Fourteen (93.3%) were initiated on a fentanyl infusion at a median of 2 mcg/kg/hr (IQR, 2–3.6), and 12 (80%) received midazolam infusions at a median of 0.06 mg/kg/hr. All patients received at least 1 IV neuromuscular blocker dose just prior to the procedure. Only 2 patients (13.3%) required an increase in their fentanyl or midazolam infusions. Procedure success was achieved in 13 patients (86.7%). Five patients (33.3%) experienced 1 cardiopulmonary AE. One patient (6.7%) had a delay in the procedure, and 1 patient (6.7%) required naloxone. Despite this, the procedure was completed in all patients. CONCLUSIONS Most received fentanyl and midazolam infusions with a dose of vecuronium just prior to the procedure. Thirteen (86.7%) met the criteria for procedure success. One-third experienced a cardiopulmonary AE. Future studies are needed to identify the optimal agents and route of administration for this procedure.

scholarly journals First-line PARP inhibitors in ovarian cancer: summary of an ESMO Open - Cancer Horizons round-table discussion

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e001110
Author(s):  
Susana Banerjee ◽  
Antonio Gonzalez-Martin ◽  
Philipp Harter ◽  
Domenica Lorusso ◽  
Kathleen N Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Round Table ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
European Medicines Agency ◽  
First Line ◽  
Phase Iii Trials

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer.

scholarly journals Genome-scale CRISPR knockout screen identifies TIGAR as a modifier of PARP inhibitor sensitivity

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Pingping Fang ◽  
Cristabelle De Souza ◽  
Kay Minn ◽  
Jeremy Chien
Keyword(s):  
Ovarian Cancer ◽  
Metabolic Pathways ◽  
Clinical Utility ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Cytotoxic Effects ◽  
Cancer Types ◽  
Genome Scale

Abstract Treatment of cancer with poly (ADP-ribose) polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination (HR) pathway. Identification of genetic targets that induce or mimic HR deficiencies will extend the clinical utility of PARP inhibitors. Here we perform a CRISPR/Cas9-based genome-scale loss-of-function screen, using the sensitivity of PARP inhibitor olaparib as a surrogate. We identify C12orf5, encoding TP53 induced glycolysis and apoptosis regulator (TIGAR), as a modifier of PARP inhibitor response. We show that TIGAR is amplified in several cancer types, and higher expression of TIGAR associates with poor overall survival in ovarian cancer. TIGAR knockdown enhances sensitivity to olaparib in cancer cells via downregulation of BRCA1 and the Fanconi anemia pathway and increases senescence of these cells by affecting metabolic pathways and increasing the cytotoxic effects of olaparib. Our results indicate TIGAR should be explored as a therapeutic target for treating cancer and extending the use of PARP inhibitors.

scholarly journals Real-world adverse events with niraparib 200 mg/day maintenance therapy in ovarian cancer: a retrospective study

2019 ◽  
Vol 15 (36) ◽  
pp. 4197-4206
Author(s):  
Jack R Gallagher ◽  
Kylee Jean Heap ◽  
Susan Carroll ◽  
Karin Travers ◽  
Brooke Harrow ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Retrospective Study ◽  
Adverse Events ◽  
Real World ◽  
Recurrent Ovarian Cancer ◽  
Medical Record Data ◽  
Platinum Based Chemotherapy ◽  
Record Data ◽  
Grade 3

Aim: To assess real-world occurrence of common clinical trial-reported adverse events (AE) among patients with recurrent ovarian cancer initiating niraparib 200 mg/day. Materials & methods: This retrospective observational study used physician-extracted anonymized medical record data of eligible patients initiating niraparib 200 mg/day after platinum-based chemotherapy. Results: Of 153 patients, 57 (37%) experienced ≥1 of the three most common all-grade AEs within 3 months after niraparib initiation: nausea (16%; grade 3/4: 2%), thrombocytopenia (14%; grade 3/4: 3%) and fatigue (24%; grade 3/4: 3%). In the ENGOT-OV16/NOVA trial, these respective AEs occurred in 74, 61 and 59% of patients. Conclusion: Incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200 mg/day in real-world practice versus patients initiating niraparib 300 mg/day in ENGOT-OV16/NOVA.

scholarly journals Niraparib in ovarian cancer: results to date and clinical potential

2017 ◽  
Vol 9 (9) ◽  
pp. 579-588 ◽  
Author(s):  
Davide Caruso ◽  
Anselmo Papa ◽  
Silverio Tomao ◽  
Patrizia Vici ◽  
Pierluigi Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Synthetic Lethality ◽  
Excision Repair ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Repair System ◽  
Gynaecological Malignancy ◽  
Platinum Based Chemotherapy ◽  
Base Excision

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.

scholarly journals The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Ni ◽  
Xianzhong Cheng ◽  
Qian Zhao ◽  
Zhiqin Dai ◽  
Xia Xu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Partial Response ◽  
Adverse Events ◽  
Cancer Patients ◽  
Real World ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Single Center ◽  
Real World Data ◽  
Platinum Based Chemotherapy

Abstract Background Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China. Methods Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. Results Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060–0.759) and disease control rate (DCR) of 50% (95%CI = 0.140–0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3–4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. Conclusion It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.

scholarly journals Comparative analysis of various obturation techniques in mandibular molars: A retrospective clinical outcome study

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 172-178
Author(s):  
Swathi U B ◽  
Sindhu Ramesh ◽  
Delphine Priscilla Antony
Keyword(s):  
Retrospective Study ◽  
Root Canal ◽  
Time Frame ◽  
Permanent Tooth ◽  
Primary Objective ◽  
Root Canal Treatment ◽  
Primary Tooth ◽  
Mandibular Molars ◽  
Significant Difference ◽  
Single Cone

The primary objective of root canal treatment is the ability to remove irritants, to clean, shape and fill the root canal system three-dimensionally and prevent recontamination from bacterial irritants. Various Obturation techniques used for filling the root canals include lateral condensation, vertical compression, and thermoplastic gutta-percha techniques. The retrospective study aimed to evaluate the various obturation techniques used in mandibular molars. For this retrospective study data collection was based on patient records of Saveetha Dental College, Chennai and consisted of a total of 1903 cases evaluated based on the obturation technique within the time frame of 10th June 2019 to 1st March 2020. In this study, the obturation technique was evaluated based on the patients age, gender, procedure and based on the tooth in which obturation was done. Inclusion criteria consisted of the tooth that underwent endodontic treatment in patients within the age group of 18 to 60 yrs, a tooth with irreversible pulpal disease or chronic apical periodontitis, permanent tooth and mandibular molars. Exclusion criteria consisted of patients above 60 years, primary tooth, teeth in which root canal treatment was not undertaken, teeth with the presence of huge periapical lesions, severely calcified canals etc., severe periodontal disease, teeth apart from mandibular molars. All the values were then statistically analysed. In this study, 1930 patients (848 are females, and 1055 were males with a mean age of 24 years) were included. It was observed in this retrospective study that there was a significant difference between the various types of obturation technique used in mandibular molars. Matched single cone obturation technique was the preferred technique of obturation in the majority of the cases (62.4%). Single cone obturation technique has advantages over other techniques of obturation due to the fewer stress forces implied apically, thereby preventing an excess of sealer extrusion.

scholarly journals Efficacy and Safety of PARP Inhibitor Combination Therapy in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Ren ◽  
Leyin Zhang ◽  
Jieru Yu ◽  
Siqi Guan ◽  
Xinyang Dai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Combination Therapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
High Grade ◽  
Efficacy And Safety

ObjectivesThough it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy.Materials and MethodsWe searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis.Results and ConclusionA total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).

scholarly journals PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”

Diagnostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 55 ◽  
Author(s):  
Boussios ◽  
Karathanasi ◽  
Cooke ◽  
Neille ◽  
Sadauskaite ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Current Evidence ◽  
Repair Pathway ◽  
Significant Efficacy

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance.

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