Phase II evaluation of nintedanib in the treatment of bevacizumab-resistant persistent/recurrent ovarian, fallopian tube, or primary peritoneal carcinoma.

Davidson, Brittany; Squatrito, Robert C.; Duska, Linda R.; Havrilesky, Laura J.; Schwager, Nyssa; McCollum, Michael; Arapovic, Sanja; Secord, Angeles Alvarez

doi:10.1200/jco.2016.34.15_suppl.tps5601

Cited by 3 publications

(2 citation statements)

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“…Indeed, a recent phase 3 trial using nintedanib (an oral triple angiokinase inhibitor of VEGF receptor, PDGFR, and fibroblast growth factor receptor), in addition to platinum based chemotherapy showed improved PFS for ovarian cancer (17.2 months vs 16.6 months; p = 0.024) [ 19 ]. Additionally, a recent phase II trial for platinum-resistant ovarian cancer patients has identified a group of patients with increased PFS after treatment with nintedanib [ 20 ]. In ICON6, the use of cediranib, another oral angiokinase inhibitor that targets VEGFR and PDGFR, in addition to platinum-based chemotherapy for platinum sensitive, recurrent ovarian cancer showed a PFS benefit of almost three months ( p < 0.0001) [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer

McDonald

Salinas

Devor

et al. 2019

IJMS

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Nearly one-third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial treatment with platinum-based therapy. Genomic and clinical characterization of these patients may lead to potential alternative therapies. Here, the objective is to classify non-responders into subsets using clinical and molecular features. Using patients from The Cancer Genome Atlas (TCGA) dataset with platinum-resistant or platinum-refractory HGSC, we performed a genome-wide unsupervised cluster analysis that integrated clinical data, gene copy number variations, gene somatic mutations, and DNA promoter methylation. Pathway enrichment analysis was performed for each cluster to identify the targetable processes. Following the unsupervised cluster analysis, three distinct clusters of non-responders emerged. Cluster 1 had overrepresentation of the stage IV disease and suboptimal debulking, under-expression of miRNAs and mRNAs, hypomethylated DNA, “loss of function” TP53 mutations, and the overexpression of genes in the PDGFR pathway. Cluster 2 had low miRNA expression, generalized hypermethylation, MUC17 mutations, and significant activation of the HIF-1 signaling pathway. Cluster 3 had more optimally cytoreduced stage III patients, overexpression of miRNAs, mixed methylation patterns, and “gain of function” TP53 mutations. However, the survival for all clusters was similar. Integration of genomic and clinical data from patients that do not respond to chemotherapy has identified different subgroups or clusters. Pathway analysis further identified the potential alternative therapeutic targets for each cluster.

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer

McDonald

Salinas

Devor

et al. 2019

IJMS

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“…A possible treatment of choice for cluster 1 could be tyrosine kinase or angiokinase inhibitors. Clinical trials with the use of nintedanib and cediranib confirmed the prolongation of PFS in patients treated with a combination of these drugs with platinum chemotherapy [8,29]. Analogically, the potential therapy for cluster 3 could be the use of deacetylase inhibitors [30].…”

Section: Genomic Signatures Of Hgstoc Cancer Cellsmentioning

confidence: 98%

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

Wilczyński,

Paradowska,

Wilczyński

2023

JPM

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High-grade serous tubo-ovarian cancer (HGSTOC) is the most lethal tumor of the female genital tract. The foregoing therapy consists of cytoreduction followed by standard platinum/taxane chemotherapy; alternatively, for primary unresectable tumors, neo-adjuvant platinum/taxane chemotherapy followed by delayed interval cytoreduction. In patients with suboptimal surgery or advanced disease, different forms of targeted therapy have been accepted or tested in clinical trials. Studies on HGSTOC discovered its genetic and proteomic heterogeneity, epigenetic regulation, and the role of the tumor microenvironment. These findings turned attention to the fact that there are several distinct primary tumor subtypes of HGSTOC and the unique biology of primary, metastatic, and recurrent tumors may result in a differential drug response. This results in both chemo-refractoriness of some primary tumors and, what is significantly more frequent and destructive, secondary chemo-resistance of metastatic and recurrent HGSTOC tumors. Treatment possibilities for platinum-resistant disease include several chemotherapeutics with moderate activity and different targeted drugs with difficult tolerable effects. Therefore, the question appears as to why different subtypes of ovarian cancer are predominantly treated based on the same therapeutic schemes and not in an individualized way, adjusted to the biology of a specific tumor subtype and temporal moment of the disease. The paper reviews the genomic, mutational, and epigenetic signatures of HGSTOC subtypes and the tumor microenvironment. The clinical trials on personalized therapy and the overall results of a new, comprehensive approach to personalized therapy for ovarian cancer have been presented and discussed.

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Prediction of Epithelial Ovarian Cancer Outcomes With Integration of Genomic Data

Newtson

Devor

Bosquet

2020

Clinical Obstetrics &Amp; Gynecology

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Some of the patients with epithelial ovarian cancer will not respond to initial therapy. These patients have a poor prognosis. Our aim was to identify patients with a worse prognosis by integrating clinical, pathologic, and genomic data. Using publicly available genomic data and integrating it with clinical data, we significantly improved the prediction of patients with worse surgical outcomes and those who do not respond to initial chemotherapy. We further improved these models with more precise data collection and better understanding of the genetic background of the studied population. Better prediction will lead to better patient classification and opportunities for individualized treatment.

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Phase II evaluation of nintedanib in the treatment of bevacizumab-resistant persistent/recurrent ovarian, fallopian tube, or primary peritoneal carcinoma.

Cited by 3 publications

References 0 publications

Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer

Molecular Characterization of Non-responders to Chemotherapy in Serous Ovarian Cancer

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?

Prediction of Epithelial Ovarian Cancer Outcomes With Integration of Genomic Data

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