767P Retrospective analysis of the impact of bevacizumab dose-intensity on the survival of platinum-resistant ovarian cancer patients

PURPOSE The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.

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The impact of dose intensity on the efficacy of gemcitabine plus carboplatin (GC) therapy for recurrent platinum-sensitive ovarian cancer (PSOC): A retrospective analysis of AGO-OVAR 2.5.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.5088 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 5088-5088

Author(s):

C. Kurzeder ◽

L. Zhao ◽

E. A. Eisenhauer ◽

I. B. Vergote ◽

A. Du Bois ◽

...

Keyword(s):

Ovarian Cancer ◽

Retrospective Analysis ◽

Dose Intensity ◽

Platinum Sensitive ◽

The Impact

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Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients

BMC Cancer ◽

10.1186/s12885-015-1104-5 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 12

Author(s):

Sigita Liutkauskiene ◽

Rasa Janciauskiene ◽

Kristina Jureniene ◽

Saulius Grizas ◽

Rasa Malonyte ◽

...

Keyword(s):

Ovarian Cancer ◽

Retrospective Analysis ◽

Dose Reduction ◽

Cancer Patients ◽

Stage Iii ◽

The Impact

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Homologous recombination deficiency and platinum rechallenge in platinum-resistant ovarian cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5576 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5576-5576 ◽

Cited By ~ 1

Author(s):

Alexandre Andre B. A. Da Costa ◽

Marcela Marinelli Salvadori ◽

Camila Vieira Valadares ◽

Carlos Stecca ◽

Louise Brot ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Homologous Recombination ◽

Cancer Patients ◽

Response Rate ◽

Homologous Recombination Deficiency ◽

Platinum Resistant ◽

Platinum Based Chemotherapy ◽

History Of ◽

The Impact

5576 Background: Ovarian carcinomas show homologous recombination deficiency (HRD) in up to 50% of cases and in 15 to 20% of cases occur due to germline BRCA1 or BRCA2 mutations. BRCA mutated tumors are more sensitive to PARP inhibitors and platinum based chemotherapy. The objective of this study was to characterize a cohort of ovarian cancer patients regarding HRD and to evaluate the impact of these scores in prolonged platinum sensitivity. Methods: Thirty one ovarian cancer patients with platinum resistant recurrence reexposed to platinum based chemotherapy were selected. Paraffin embedded tumor samples from 14 patients were analyzed using ONCOSCAN assay (Affymetrix) to evaluate HRD scores. The association of the scores with response rate to platinum rechallenge, overall survival and clinical pathologic factors was evaluated. Results: From the cohort of 31 patients, 15 samples from 14 patients were analyzed for genomic alterations. Median scores were 19.5 for TAI, 12.5 for cnLOH+L, 26.0 for LST and 6.3 for HRD. High scores were found in 10 out of 14 (for cnLOH+L score) and 9 out of 14 (for LST score) patients. Seven of the 14 patients analyzed analyzed for genomic alterations had response, which suggested homologous recombination deficiency. No significant differences were observed between response rates for high versus low scores. Numerically, cnLOH+L, LST and HDR scores were higher in patients with response to treatment compared to those without response. Median overall survival was 13.4 months from the beginning of platinum rechallenge and no difference in survival according to scores was observed. Among the clinical pathologic factors, family history of breast or ovarian cancer or personal history of breast cancer was associated to higher response rate to platinum rechallenge. Conclusions: In conclusion,HRD scores showed to be potential markers of response to platinum rechallenge in the platinum resistant setting. Further studies are necessary to clarify the best cutoffs for each score, the impact of tumor heterogeneity and the analysis of tumor samples in the moment of treatment. Positive family history of cancer is a clinical factor predictvie of platinum rechallenge response.

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The impact of obesity on treatment and outcomes in ovarian cancer by race/ethnicity.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18067 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18067-e18067

Author(s):

Alexandra Martin ◽

Adrianne Rose Mallen ◽

Sweta Sinha ◽

Ali Wells ◽

Kathryn Cline ◽

...

Keyword(s):

Ovarian Cancer ◽

Dose Reduction ◽

Cancer Patients ◽

Tertiary Care ◽

Dose Intensity ◽

Comprehensive Cancer Center ◽

Increased Risk ◽

Race Ethnicity ◽

Similar Survival ◽

The Impact

e18067 Background: Concern for toxicities in obese ovarian cancer patients may limit weight-based chemotherapy dosing, which has been associated with poor survival. We sought to evaluate the impact of obesity on treatment and outcomes by race/ethnicity at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center (CCC). Methods: 66 minority (non-Hispanic black, Hispanic) epithelial ovarian cancer patients diagnosed 2006 and treated with frontline chemotherapy were frequency matched to two non-Hispanic white (NHW) patients by 5-year age group and stage (n = 198). For frontline carboplatin, relative dose intensity (RDI) was calculated by dividing the dose received by the expected dose, with an RDI < 0.85 indicating carboplatin dose reduction. Patient characteristics and RDI were compared by obesity and race/ethnicity. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between obesity, race/ethnicity and RDI with mortality, adjusting for confounders. Results: Minorities were more likely to be obese, underinsured, and to experience delays in chemotherapy compared to NHW. Compared to normal/overweight patients, obese patients were more likely to experience carboplatin under dosing in the neoadjuvant (p = 0.004) and adjuvant (p < 0.0001) setting, but there were no differences in RDI by race/ethnicity or toxicities. No association with survival was observed for dose reduction and BMI. Compared to NHW, minorities had similar survival in the first 4 years after diagnosis (HR = 0.99, 95% CI = 0.60-1.63), but an increased risk of mortality > 4 years after diagnosis (HR = 4.07, 95% CI = 1.92, 8.60). Conclusions: Even though minorities were more likely to be obese, there were no differences in dosing by race/ethnicity at an NCI CCC. Minorities had similar survival to NHW in the first 4 years after diagnosis, likely due to similar access to quality care at an NCI CCC. However, > 4 years after diagnosis, the racial/ethnic survival disparity persisted after adjustment for clinical and pathologic characteristics. Expansion of this work to other patient populations may help determine if findings are similar outside of a tertiary care center.

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RETROSPECTIVE ANALYSIS OF THE IMPACT OF PLATINUM DOSE MODIFICATIONS ON THE OUTCOMES OF STAGE I-IV OVARIAN CANCER PATIENTS

10.26226/morressier.599bdc7cd462b80296ca14dd ◽

2017 ◽

Author(s):

Sigita Liutkauskiene

Keyword(s):

Ovarian Cancer ◽

Retrospective Analysis ◽

Cancer Patients ◽

Stage I ◽

Dose Modifications ◽

The Impact

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A retrospective analysis of immunohistochemically determined IRF4 (interferon regulating factor 4) expression in a consecutive cohort of 114 ovarian cancer patients

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-018-4941-z ◽

2018 ◽

Vol 299 (1) ◽

pp. 239-246 ◽

Cited By ~ 1

Author(s):

Anne-Sophie Heimes ◽

Marcus Schmidt ◽

Joerg Jäkel ◽

Katrin Almstedt ◽

Susanne Gebhard ◽

...

Keyword(s):

Ovarian Cancer ◽

Retrospective Analysis ◽

Cancer Patients

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Extracellular vesicle-associated miRNAs in ovarian cancer – design of an integrated NGS-based workflow for the identification of blood-based biomarkers for platinum-resistance

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-1048 ◽

2019 ◽

Vol 57 (7) ◽

pp. 1053-1062 ◽

Cited By ~ 14

Author(s):

Jan Dominik Kuhlmann ◽

Issam Chebouti ◽

Rainer Kimmig ◽

Paul Buderath ◽

Michael Reuter ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Independent Set ◽

Extracellular Vesicle ◽

Platinum Resistance ◽

Diagnostic Purpose ◽

Illumina Platform ◽

Platinum Sensitive ◽

Platinum Resistant ◽

Next Generation Sequencing Ngs

AbstractBackgroundExtracellular vesicle (EV)-associated microRNAs (miRNAs) have been suggested as promising biomarkers for blood-based cancer diagnosis. However, one of the major limitations for the use of EVs with diagnostic purpose is the lack of standardized EV-profiling techniques. In this regard, the objective of our study was to design an integrated next-generation sequencing (NGS)-based workflow for analyzing the signature of EV-associated miRNA in the plasma of platinum-resistant ovarian cancer patients.MethodsFor EV-extraction, different enrichment methods were compared (ExoQuick vs. exoRNeasy). NGS was performed with the Illumina platform.ResultsWe established an integrated NGS-based workflow, including EV-enrichment with the ExoQuick system, which resulted in an optimal RNA-yield and consistent small RNA libraries. We applied this workflow in a pilot cohort of clinically documented platinum-sensitive (n=15) vs. platinum-resistant (n=15) ovarian cancer patients, resulting in a panel of mature EV-associated miRNAs (including ovarian cancer associated miR-181a, miR-1908, miR-21, miR-486 and miR-223), which were differentially abundant in the plasma of platinum-resistant patients.ConclusionsThis is the first study, analyzing the profile of EV-associated miRNAs in platinum-resistant ovarian cancer patients. We provide rationale to further validate these miRNA candidates in an independent set of patients, in order to characterize their biomarker potential as predictors for platinum-resistance.

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355 Pembrolizumab and bevacizumab in platinum resistant epithelial ovarian cancer patients

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.355 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A382-A382

Author(s):

Judith Michels ◽

Jean-Sebastien Frenel ◽

Catherine Genestie ◽

François Ghiringhelli ◽

Caroline Brard ◽

...

Keyword(s):

Ovarian Cancer ◽

Clin Oncol ◽

Cancer Patients ◽

Bowel Perforation ◽

Phase Iii ◽

Antiangiogenic Agents ◽

List Type ◽

Open Label ◽

Platinum Resistant ◽

Flat Dose

BackgroundThere is a medical need in platinum resistant ovarian cancer patients. Median progression-free survival (PFS) is 3.4 months with chemotherapy and 6.7 months with chemotherapy-bevacizumab combination regimens.1 RECIST overall response rate (ORR) is 11.8% and 27.3%, respectively. The ORR is 15.9% for bevacizumab as a monotherapy with a median PFS of 4.4 months.2MethodsNCT03596281 An open-label phase 1b trial with a modified toxicity probability interval design to evaluate the combination of a flat dose of 400mg bevacizumab for 6 cycles and 200mg pembrolizumab until disease progression, unacceptable toxicity or completed 24 months of treatment in patients with platinum resistant ovarian cancer. The primary evaluation criteria is safety, the secondary endpoint is the efficacy.Results19 patients have been enrolled between January 2019 and February 2021 in 6 French centers. Patients‘ characteristics are reported (table 1). No dose limiting toxicities were observed. Grade 3 treatment related adverse events occurred in 3 patients (i.e. arterial thromboembolism, bowel perforation, proteinuria and sepsis). No grade 4/5 toxicities were induced. A median of 7 cycles (range 3–14) were administered. Median follow-up of patients was 4.1 months (1.8–23). The RECIST ORR was 26.3% (1 complete response and 4 partial responses) (table 2). The disease control rate was 78.9%. The time to progression was not yet reached in 6 patients. The ORR was equivalent whether patients have been pretreated or not with bevacizumab (27.3 and 25% respectively) (table 3). The ORR according to the combined positive score (CPS) for the evaluation of PD-L1 was 50.0% for CPS≥10% (n=4), 30.0% for a CPS≥1% (n=10) and 25.0% for CPS<1 (n=8) (table 4).ConclusionsA chemotherapy-free regimen combining pembrolizumab and bevacizumab was well tolerated and showed encouraging results in heavily pretreated platinum resistant ovarian cancer patients independent of their previous challenge with antiangiogenic agents.AcknowledgementsFunding for this research was provided by Fondation Cancer du Luxembourg and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT03596281ReferencesPujade-Lauraine E, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Onco Off J Am Soc Clin Oncol 32,1302–1308 (2014).Cannistra SA, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol Off J Am Soc Clin Oncol 33,5180–5186 (2007).Ethics ApprovalThis study was approved by CPP Sud Méditerranée V institution’s Ethics Board; approval number 18.020 (EudraCT number 2017-004197-34).ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

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