Outcomes of ovarian cancer patients treated with platinum or non-platinum based chemotherapy after PARP inhibitor maintenance.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5563-5563
Author(s):  
Ralynn Brann ◽  
Kevin Michael Kremer ◽  
Matthew Carlson ◽  
Salvatore LoCoco ◽  
Jayanthi Sivasothy Lea ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Treatment Time ◽  
Statistical Tests ◽  
Parp Inhibitor ◽  
Tertiary Care ◽  
Platinum Resistance ◽  
Time To Progression ◽  
Front Line ◽  
Platinum Based Chemotherapy

5563 Background: PARP inhibitors (PARPi) are approved for maintenance treatment of platinum sensitive ovarian cancers either after front-line therapy or after treatment for recurrence. Current recommendations include retreatment with platinum-based chemotherapy (PC) after progression on maintenance PARPi. There exists a theoretical concern that progression of disease (POD) on PARPi is indicative of the development of platinum resistance due to similar DNA targets of platinum chemotherapy and PARPi. Our objective was to evaluate the response to subsequent chemotherapy in patients who progressed on PARPi maintenance. Methods: All patients with ovarian, fallopian tube, or primary peritoneal cancer treated with PARPi treatment from 2017 to 2021 at two academic tertiary care centers were retrospectively identified. Patients were assessed for treatment time on PARPi, time to POD on PARPi (PFS), type of chemotherapy regimen following PARPi maintenance, and time to disease progression on subsequent therapy following PARPi (PFS2). Comparative statistical analyses were performed with appropriate two-sided statistical tests. Time to progression on chemotherapy after PARPi was calculated using the Kaplan-Meier method. Results: A total of 83 ovarian cancer patients treated with PARPi were identified, and of these, 61 (73.5%) were treated with PARPi in the maintenance setting. Among the patients treated with PARPi maintenance, 22 (36.1%) remain on treatment. 19 (31.1%) patients were started on PARPi maintenance after front-line chemotherapy. While on PARPi maintenance, 63.9% discontinued PARPi, the majority due to POD, and 26.2% due to patient intolerance of side effects. Following POD, 21/29 (72.4%) received subsequent PC and 8/29 (27.6%) received non-platinum based chemotherapy (NPC). Treatment time, PFS, and PFS2 are listed in Table. Of the patients who received PC, 14/21 (66.7%) had a PFS2 of over six months and 5/21 (23.8%) had a PFS2 of over 12 months. Of the patients who received NPC, 7/8 (87.5%) had a PFS2 of over six months and 2/8 (25.0%) had a PFS2 of over 12 months. Conclusions: Following POD on PARPi, patients responded to both PC and NPC. Time to progression on subsequent chemotherapy after treatment with PARPi does not differ significantly between PC and NPC regimens. Many patients continue to see benefit from PC after PARPi maintenance. Retreatment with PC following POD on PARPi maintenance should still be considered.[Table: see text]

New biomarkers to predict platinum resistance in ovarian cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17085-e17085
Author(s):  
Oana Trifanescu ◽  
Laurentia Minea Gales ◽  
Maria Iuliana Gruia ◽  
Bianca Andreea Gusoiu ◽  
Florina Torliceanu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Roc Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Initial Response ◽  
Platinum Resistance ◽  
Platinum Sensitive ◽  
Platinum Salts ◽  
Platinum Based Chemotherapy

e17085 Background: Epithelial ovarian cancer is the second most common gynecologic malignancy and is characterized by the highest mortality of all gynecological cancers. Despite of initial response, platinum resistance develops and contributes to the poor outcome of advanced stage ovarian cancer patients. The aim of the study was to identify biomarkers helpful in predicting treatment response to platinum salts. Methods: Forty eight patients with advanced ovarian (stage II, III and IV) cancer were prospectively enrolled between 2014 and 2017. All patients underwent surgery followed by platinum-based chemotherapy. Serum reactive oxygen species parameters such as malondialdehyde, ceruloplasmine, and serum VEGF were measured before each cycle of chemotherapy. Results: Mean age at diagnostic was 51.3 +/- 8.1 years, (range 42 - 78). Median follow up was 39 months (range 12-56). Twenty tree percent were platinum resistance. Median progression free survival was 22 months and estimated median overall survival was 84 months, 77% of patients being alive at 3 years. VEGF levels were significantly higher in patients with platinum resistance disease (1210 pg/ml) compare to platinum sensitive (mean VEGF levels 945pg/ml, p = 0.0003). We used a ROC curve to estimate the sensitivity and specificity of VEGF as a predictor to platinum response and find out that the aria under the curve (AUC) was 0.874, p = 0.003, 95% CI 0.734-1 and cut-off value (80% sensibility, 80% specificity) was 1085pg/ml. Malondialdehyde levels were statistically significant higher in patients with platinum resistance disease (mean value 11.1 μmol/100 ml vs. 7.4 μmol/100 ml in platinum sensitive, p = 0.02. The ROC curve for malondialdehyde identify an aria under the curve of 0.818, p = 0.0001 and CI 95% (0.744-0.893) and a cut-off value of 7.74 μmol/100 ml to estimate with 81.3% sensitivity and 64% specificity platinum response validating this bio markers as predicting platinum response. For Ceruloplasmine AUC was 0.706, p = 0.0001, 95% CI (0.617,-0.796). Conclusions: Malondialdehyde, ceruloplasmine and VEGF can estimate with precision the resistance to platinum salts in advanced ovarian cancer patients.

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.

Serum calretinin as a predictor for recurrence and overall survival in ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17033-e17033
Author(s):  
Pauline Wimberger ◽  
Simon Passek ◽  
Theresa Link ◽  
Yana Vassileva ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Calcium Binding ◽  
Tumor Resection ◽  
High Volume ◽  
Primary Diagnosis ◽  
Platinum Resistance ◽  
Serum Samples ◽  
Platinum Based Chemotherapy

e17033 Background: Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed, herein. Methods: Serum calretinin (sCRT) was determined by calretinin enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n = 115 (86%) with FIGO III or IV), including samples at primary diagnosis and at 4 follow-up reading points in the course of adjuvant treatment. Results: sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED = 0.3ng/ml, p < 0.001) and enabled an accurate discrimination between ovarian cancer and controls (AUC = 0.85). High sCRT levels at primary diagnosis predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p < 0.001) and were associated with advanced FIGO-stage (p < 0.001) and high volume of ascites (p < 0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR:1.99, p = 0.018) and also indicated poor OS (HR:2.49, p = 0.008). Increased sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR:15.4, p = 0.01; HR:5.59, p = 0.026). Moreover, elevated sCRT levels at primary diagnosis indicated platinum-resistance (p = 0.002). Conclusions: This is the first study, suggesting sCRT as an innovative liquid biopsy marker for ovarian cancer by showing its independent prognostic relevance and its association with primary platinum-resistance.

scholarly journals How to sequence treatment in relapsed ovarian cancer

2020 ◽  
Author(s):  
Sandro Pignata ◽  
Sabrina Chiara Cecere
Keyword(s):  
Ovarian Cancer ◽  
Recurrent Disease ◽  
Recurrent Ovarian Cancer ◽  
Platinum Resistance ◽  
Front Line ◽  
Related Factors ◽  
Drug Classes ◽  
Stage Disease ◽  
Platinum Based Chemotherapy ◽  
Line Setting

Numerous disease- and patient-related factors must be considered when selecting systemic therapy for recurrent ovarian cancer. Anti-angiogenics (bevacizumab) and poly(ADP-ribose) polymerase inhibitors (olaparib, niraparib, rucaparib) have an important role as maintenance of platinum-based chemotherapy for recurrent disease and their use in the first-line setting of advanced-stage disease is becoming established. As previous exposure to none, one or both of these drug classes is integral to selecting next therapy, front-line use impacts on options available to treat recurrent disease. A key strategy to delay platinum resistance and improve prognosis of recurrent disease is to alternate treatments with different mechanisms of action. The multiple mechanisms of trabectedin and its complementarity with platinum allow intercalation between platinum regimens in potentially platinum-responsive patients with recurrent disease.

scholarly journals The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China

2020 ◽  
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 ◽  
Advanced Ovarian Cancer ◽  
Real World Data ◽  
Platinum Based Chemotherapy

Abstract BackgroundNiraparib, 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) positive. We present real-world experience from China. MethodsPatients 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. ResultsTwenty-two patients all received niraparib at an bolus of 200mg/d. 50% 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 DCR of 50% (95%CI=0.140-0.861) in the exploratory multi-line monotherapy group. Commonly 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. ConclusionIt is feasible for patients received a bolus of 200mg/d in Chinese population with promising efficacy and well tolerated. This is first real world data about niraparib in ovarian cancer patients with HRD status from China.

ERCC1 Genotype and Phenotype in Epithelial Ovarian Cancer Identify Patients Likely to Benefit From Paclitaxel Treatment in Addition to Platinum-Based Therapy

2007 ◽  
Vol 25 (33) ◽  
pp. 5172-5179 ◽  
Author(s):  
Stephanie Smith ◽  
Dan Su ◽  
Irene A. Rigault de la Longrais ◽  
Peter Schwartz ◽  
Manuela Puopolo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Treatment Response ◽  
Cancer Patients ◽  
Excision Repair ◽  
Platinum Resistance ◽  
Platinum Based Chemotherapy ◽  
Risk Of Disease ◽  
Ercc1 Expression

Purpose To investigate the effect of excision repair cross-complementation group 1 (ERCC1) on treatment response and survival of patients treated with platinum chemotherapy with or without paclitaxel. Patients and Methods Tumor samples from epithelial ovarian cancer patients were evaluated for ERCC1 mRNA expression and a single nucleotide polymorphism at codon 118 (C>T). Of 178 patients treated with postoperative platinum-based chemotherapy, 75 were also given paclitaxel. For all of these patients, ERCC1 expression and genotype were analyzed for associations with treatment response and survival. Results Among the 103 patients treated with platinum without paclitaxel, the C/C genotype, compared with C/T and T/T, was associated with greater risk of disease progression and death (hazard ratio [HR], 1.95, P = .051; HR, 2.01, P = .033, respectively); high levels of ERCC1 mRNA, compared with low levels, were associated with greater risk of disease progression (HR, 2.41; P = .014). Similarly, when the ERCC1 data were combined, patients with the C/C genotype and high ERCC1 expression had greater risk for disease progression (HR, 3.73; P = .003) compared with those with low expression and non-C/C genotype. However, for the 75 patients treated with platinum plus paclitaxel, the C/C genotype and high ERCC1 expression were not associated with poor prognosis, suggesting that paclitaxel may help to alleviate ERCC1-related platinum resistance. Conclusion Ovarian cancer patients with high ERCC1 expression or the C/C genotype at codon 118 may benefit from the combination of platinum and paclitaxel, while those with low ERCC1 expression or the C/T or T/T genotype may respond well to platinum without paclitaxel.

scholarly journals Long-Term Follow-Up of a Female Patient Treated with Olaparib—Hope for a Long Life without Relapse?

2021 ◽  
Vol 18 (7) ◽  
pp. 3430
Author(s):  
Mateusz Kozłowski ◽  
Katarzyna Nowak ◽  
Aneta Cymbaluk-Płoska
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
Brca1 Gene ◽  
High Specificity ◽  
Reproductive Organs ◽  
Platinum Based Chemotherapy ◽  
Long Term Follow Up ◽  
History Of ◽  
Advanced Stages

Ovarian cancer is one of the most common cancers of the reproductive organs. As there are no symptoms in the early stages, it is mainly detected in the advanced stages. Even then, the symptoms are non-specific and include, for example, abdominal pain, early satiety, or changes in bowel habits. Both biochemical marker levels and imaging studies are used in the initial diagnosis. However, it should be emphasized that they are not characterized by high specificity. Treatment is multistage, and usually first-line debulking surgery is used followed by platinum-based chemotherapy. Here we present a clinical case of a 56-year-old female, a carrier of a mutation in the BRCA1 gene, with a history of breast cancer and with recurrent epithelial ovarian cancer. The patient was qualified for treatment with a PARP inhibitor and is currently undergoing treatment with olaparib. In the patient’s follow up of 50 months to date, there has been no recurrence of cancer. Few side effects have been observed, and the most serious one that can be effectively treated is anemia. On the basis of the described case, the authors concluded that olaparib treatment is effective, relatively safe, and does not significantly affect daily functioning.

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