GEICO1601-ROLANDO: A Multicentric Single Arm Phase II Clinical Trial to Evaluate the Combination of Olaparib and Pegylated Liposomal Doxorubicin for Platinum-Resistant Ovarian Cancer

Pérez-Fidalgo, J.A.; Iglesias, María; Bohn, Uriel; Calvo, E.; García, Yolanda; Guerra, Eva; Manso, Luis; Santaballa, Ana; González-Martín, Antonio

doi:10.4155/fsoa-2018-0107

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…Even in heavily pretreated PR-ROC, ORR was 22.9% for olaparib versus 0% for CHT. mPFS in PR-ROC was not significantly improved (Perez-Fidalgo et al, 2019;Vanderstichele et al, 2022).…”

Section: Future Perspectives and Conclusionmentioning

confidence: 76%

Olaparib and advanced ovarian cancer: Summary of the past and looking into the future

Maiorano

Maiello

2023

Front. Pharmacol.

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Ovarian cancer (OC) is women’s eighth most common cancer, bearing the highest mortality rates of all female reproductive system malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPis) have reshaped the treatment scenario of metastatic OC as a maintenance post platinum-based chemotherapy. Olaparib is the first PARPi developed for this disease. Results from Study 42, Study 19, SOLO2, OPINION, SOLO1, and PAOLA-1 clinical trials, led to the FDA and EMA approval of olaparib for the maintenance treatment of women with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer without platinum progression: in the platinum-sensitive recurrent OC; in the newly diagnosed setting in case Breast Cancer (BRCA) mutations and, in combination with bevacizumab, in case of BRCA mutation or deficiency of homologous recombination genes. In this review, we synthetized olaparib’s pharmacokinetic and pharmacodynamic properties and its use in special populations. We summarized the efficacy and safety of the studies leading to the current approvals and discussed the future developments of this agent.

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“…Even in heavily pretreated PR-ROC, ORR was 22.9% for olaparib versus 0% for CHT. mPFS in PR-ROC was not significantly improved (Perez-Fidalgo et al, 2019;Vanderstichele et al, 2022).…”

Section: Future Perspectives and Conclusionmentioning

confidence: 76%

Olaparib and advanced ovarian cancer: Summary of the past and looking into the future

Maiorano

Maiello

2023

Front. Pharmacol.

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“…It has been previously shown that the cytotoxic effects of olaparib can be increased by concomitant treatment with DNA-damaging agents such as doxorubicin [ 32 ]. To test the impact of a DNA damaging agent in the presence of entinostat and olaparib we quantified the number of DNA DSBs by staining of the phosphorylated histone variant γH2A.X after 24 h of treatment with entinostat, olaparib and doxorubicin in single, double and triple drug treatment.…”

Section: Resultsmentioning

confidence: 99%

“…with doxorubicin) may be beneficial to fully exploit the reduced DDR capacity of cells treated with entinostat and olaparib. The combination of PARPi with a DNA-damaging chemotherapy is already being investigated in adult (NCT03161132; NCT00740805) and pediatric clinical trials (NCT02813135; NCT03749187; NCT02044120) [ 32 , 49 ]. Importantly in the field of neuro-oncology several trials investigate PARPi treatment in combination with radiotherapy and/or temozolomide in HGG (NCT03581292; NCT03212742; NCT03749187).…”

Section: Discussionmentioning

confidence: 99%

Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells

Vollmer,

Ecker,

Hielscher

et al. 2023

J Neurooncol

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Purpose MYC-driven Group 3 medulloblastoma (MB) (subtype II) is a highly aggressive childhood brain tumor. Sensitivity of MYC-driven MB to class I histone deacetylase inhibitors (HDACi) has been previously demonstrated in vitro and in vivo. In this study we characterize the transcriptional effects of class I HDACi in MYC-driven MB and explore beneficial drug combinations. Methods MYC-amplified Group 3 MB cells (HD-MB03) were treated with class I HDACi entinostat. Changes in the gene expression profile were quantified on a microarray. Bioinformatic assessment led to the identification of pathways affected by entinostat treatment. Five drugs interfering with these pathways (olaparib, idasanutlin, ribociclib, selinexor, vinblastine) were tested for synergy with entinostat in WST-8 metabolic activity assays in a 5 × 5 combination matrix design. Synergy was validated in cell count and flow cytometry experiments. The effect of entinostat and olaparib on DNA damage was evaluated by γH2A.X quantification in immunoblotting, fluorescence microscopy and flow cytometry. Results Entinostat treatment changed the expression of genes involved in 22 pathways, including downregulation of DNA damage response. The PARP1 inhibitors olaparib and pamiparib showed synergy with entinostat selectively in MYC-amplified MB cells, leading to increased cell death, decreased viability and increased formation of double strand breaks, as well as increased sensitivity to additional induction of DNA damage by doxorubicin. Non-MYC-amplified MB cells and normal human fibroblasts were not susceptible to this triple treatment. Conclusion Our study identifies the combination of entinostat with olaparib as a new potential therapeutic approach for MYC-driven Group 3 MB.

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“…PARP inhibitors as single agents have shown very modest activity in platinum-resistant OC patients in a BRCA-non selected population. The ongoing GEICO1601-ROLANDO trial is a protocol designed with the aim of assessing efficacy and safety of the combination of olaparib and PLD followed by olaparib maintenance in such setting [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Predicting Response to Anthracyclines in Ovarian Cancer

Ferrero

Borghese²,

Restaino

et al. 2022

IJERPH

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(1) Background: Anthracyclines are intriguing drugs, representing one of the cornerstones of both first and subsequent-lines of chemotherapy in ovarian cancer (OC). Their efficacy and mechanisms of action are related to the hot topics of OC clinical research, such as BRCA status and immunotherapy. Prediction of response to anthracyclines is challenging and no markers can predict certain therapeutic success. The current narrative review provides a summary of the clinical and biological mechanisms involved in the response to anthracyclines. (2) Methods: A MEDLINE search of the literature was performed, focusing on papers published in the last two decades. (3) Results and Conclusions: BRCA mutated tumors seem to show a higher response to anthracyclines compared to sporadic tumors and the severity of hand–foot syndrome and mucositis may be a predictive marker of PLD efficacy. CA125 can be a misleading marker of clinical response during treatment with anthracyclines, the response of which also appears to depend on OC histology. Immunochemistry, in particular HER-2 expression, could be of some help in predicting the response to such drugs, and high levels of mutated p53 appear after exposure to anthracyclines and impair their antitumor effect. Finally, organoids from OC are promising for drug testing and prediction of response to chemotherapy.

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GEICO1601-ROLANDO: A Multicentric Single Arm Phase II Clinical Trial to Evaluate the Combination of Olaparib and Pegylated Liposomal Doxorubicin for Platinum-Resistant Ovarian Cancer

Cited by 8 publications

References 14 publications

Olaparib and advanced ovarian cancer: Summary of the past and looking into the future

Olaparib and advanced ovarian cancer: Summary of the past and looking into the future

Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells

Predicting Response to Anthracyclines in Ovarian Cancer

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