Real-world treatment patterns and outcomes in platinum-sensitive recurrent high-grade serous ovarian cancer patients

Aim: To describe the overall cancer-related healthcare utilization patterns, treatment patterns and outcomes in women diagnosed with platinum-sensitive recurrent high-grade serous ovarian cancer. Patients & methods: Subanalysis of the Spanish sample of a retrospective, noninterventional, multinational, observational study. Results: BRCA-mutated patients had better outcomes in terms of progression-free survival and overall survival than patients who were BRCA wild-type. It was observed that patients’ treatment outcomes after the first recurrence progressively worsened as the patient underwent subsequent chemotherapy lines. Healthcare resource utilization when accounting for the follow-up time did not substantially differ between BRCA1/ 2-mutated and BRCA wild-type patients. Conclusion: BRCA1/2 mutation carriers have better treatment outcomes, including longer survival, without a negative impact on the use of healthcare resources.

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Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study

Biomedicines ◽

10.3390/biomedicines9010055 ◽

2021 ◽

Vol 9 (1) ◽

pp. 55

Author(s):

Francesco Plotti ◽

Corrado Terranova ◽

Federica Guzzo ◽

Carlo De Cicco Nardone ◽

Daniela Luvero ◽

...

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Predictive Marker ◽

Chemotherapy Response ◽

High Grade ◽

Serous Ovarian Cancer ◽

Wild Type ◽

Platinum Sensitive ◽

Platinum Resistant

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.

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Meta-analysis on the PARP-inhibitor olaparib reveals therapeutic efficacy in ovarian cancer independent of BRCA1/2 mutation status

Advances in Modern Oncology Research ◽

10.18282/amor.v2.i2.54 ◽

2016 ◽

Vol 2 (2) ◽

pp. 91 ◽

Cited By ~ 1

Author(s):

Ines Vasconcelos ◽

Oscar Gaspar

Keyword(s):

Ovarian Cancer ◽

Clinical Trials ◽

Cancer Patients ◽

Fallopian Tube ◽

Parp Inhibitor ◽

Parp Inhibitors ◽

High Grade ◽

Wild Type ◽

Mutation Status ◽

Platinum Sensitive

<div>Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising drugs for ovarian cancer treatment. This study investigated clinical trials of PARP inhibitors, in order to obtain a more complete prognosis of ovarian cancer patients, which is usually dependent on their BRCA1/2 mutation status. The PubMed database was searched using the key terms “PARP inhibitor OR olaparib OR veliparib OR niraparib OR rucaparib OR (BMN 673) AND (ovarian cancer OR solid tumors)”, while narrowing the selection of the article type to “clinical trial” only. Women included in the study had been histologically diagnosed with recurrent high-grade serous ovarian-, fallopian tube- or primary peritoneal-carcinoma, regardless of the presence of BRCA germline mutation or platinum-sensitive disease recurrence. Data from three Phase I and eight Phase II clinical trials were obtained, two of which evaluated veliparib, eight olaparib and one niraparib. A total of 1042 patients with either high-grade serous ovarian-, fallopian tube- or primary peritoneal cancer were enrolled, of which 587 had a BRCA1/2 germline mutation and at least 370 were platinum-sensitive. The overall response rate (ORR) for patients who underwent treatment with olaparib was 44.5% (95% confidence interval = 0.396–0.496). Patients with BRCA1/2 mutation and those with wild-type BRCA1/2 showed no significant difference in ORR (p = 0.35), even when considering solely Phase II trials (p = 0.13). PARP inhibitors, particularly olaparib, proved effective in the management of ovarian cancer patients. This study identified the existence of patients who presented wild-type BRCA1/2 and possibly BRCA-independent homologous-recombination deficient tumors, or patients with wild-type BRCA1/2 and tumors presenting other forms of BRCAness, who benefit from treatment with olaparib.</div>

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SHOULD AROMATASE INHIBITORS BE USED AS MAINTENANCE TREATMENT IN HIGH-GRADE SEROUS OVARIAN CANCER PATIENTS?

10.26226/morressier.599bdc7ad462b80296ca1822 ◽

2017 ◽

Author(s):

Alexandra Maria Knipprath-Mészáros

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Aromatase Inhibitors ◽

Maintenance Treatment ◽

High Grade ◽

Serous Ovarian Cancer

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Molecular predictors of the outcome of paclitaxel plus carboplatin neoadjuvant therapy in high-grade serous ovarian cancer patients

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04301-6 ◽

2021 ◽

Author(s):

Anna P. Sokolenko ◽

Tatiana V. Gorodnova ◽

Ilya V. Bizin ◽

Ekaterina Sh. Kuligina ◽

Khristina B. Kotiv ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

High Grade ◽

Serous Ovarian Cancer

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Development of a Genomic Signatures-Based Predictor of Initial Platinum-Resistance in Advanced High-Grade Serous Ovarian Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2020.625866 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yuan Li ◽

Xiaolan Zhang ◽

Yan Gao ◽

Chunliang Shang ◽

Bo Yu ◽

...

Keyword(s):

Ovarian Cancer ◽

Predictive Accuracy ◽

Predictive Performance ◽

Platinum Resistance ◽

High Grade ◽

Serous Ovarian Cancer ◽

Single Nucleotide Variants ◽

Tissue Samples ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet.MethodsNinety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients.ResultsA high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1–100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%.ConclusionsA multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

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