Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer

Colombo, Nicoletta; Tomao, Federica; Panici, Pierluigi Benedetti; Nicoletto, Maria Ornella; Tognon, Germana; Bologna, Alessandra; Lissoni, Andrea Alberto; DeCensi, Andrea; Lapresa, Mariateresa; Mancari, Rosanna; Palaia, Innocenza; Tasca, Giulia; Tettamanzi, Francesca; Alvisi, M.F.; Rulli, Eliana; Poli, Davide; Carlucci, Luciano; Torri, V.; Fossati, Roldano; Biagioli, Elena

doi:10.1016/j.ygyno.2022.01.015

Cited by 36 publications

(38 citation statements)

References 18 publications

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“…Although the recent GY004 phase III (NCT02446600) study demonstrated similar activity with cediranib plus olaparib compared to standard-of-care (SOC) chemotherapy in platinum sensitive recurrent EOC, the study did not meet the primary endpoint of improved PFS with median PFS of 10.3, 8.2 and 10.4 months for SOC chemotherapy, olaparib monotherapy and cediranib/olaparib combination respectively [ 52 ]. The combination of olaparib and cediranib has also been evaluated in platinum resistant disease in the BAROCCO (NCT03314740) and OCTOVA (NCT03117933) and AMBITION (NCT03699449) clinical trials [ 53 54 55 ]. Whilst no significant improvement in PFS was observed with either continuous or intermittent cediranib with olaparib compared with weekly paclitaxel within BAROCCO, continuous administration demonstrated a trend for improved PFS compared to chemotherapy (5.8 months vs. 3.1 months, hazard ratio [HR]=0.76; 90% confidence interval [CI]=0.50–1.14) [ 53 ].…”

Section: Molecularly Targeted Agentsmentioning

confidence: 99%

“…The combination of olaparib and cediranib has also been evaluated in platinum resistant disease in the BAROCCO (NCT03314740) and OCTOVA (NCT03117933) and AMBITION (NCT03699449) clinical trials [ 53 54 55 ]. Whilst no significant improvement in PFS was observed with either continuous or intermittent cediranib with olaparib compared with weekly paclitaxel within BAROCCO, continuous administration demonstrated a trend for improved PFS compared to chemotherapy (5.8 months vs. 3.1 months, hazard ratio [HR]=0.76; 90% confidence interval [CI]=0.50–1.14) [ 53 ]. In the OCTOVA trial, cediranib and olaparib treatment significantly increased PFS compared to olaparib monotherapy (median PFS 5.4 vs. 3.7 months, HR=0.70; 95% CI=0.57–0.86) and was numerically superior to weekly paclitaxel (median PFS 3.9 months), although the trial was not designed to compare these treatment arms directly [ 55 ].…”

Section: Molecularly Targeted Agentsmentioning

confidence: 99%

“…These studies suggest as treatment, PARPi combination with antiangiogenic agents demonstrates efficacy based on objective response rates and PFS [ 53 55 56 ]. Whilst combination therapy has not been shown to be superior to SOC chemotherapy, based on toxicity and patient preferences it may provide a viable option as a chemotherapy sparing regime.…”

Section: Molecularly Targeted Agentsmentioning

confidence: 99%

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PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies

2022

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The use of PARP inhibitors (PARPi) in patients with epithelial ovarian cancer is expanding, with the transition from use in recurrent disease to the first-line setting. This is accompanied with an increasing population of patients who develop acquired PARPi resistance. Coupled with those patients with primary PARPi resistance, there is an urgent need to better understand mechanisms of resistance and identify means to overcome this resistance. Combination therapy offers the potential to overcome innate and acquired resistance, by either working synergistically with PARPi or by restoring homologous recombination deficiency, targeting the homologous recombination repair pathway through an alternate strategy. We discuss mechanisms of PARPi resistance and data on novel combinations which may restore PARPi sensitivity.

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Section: Molecularly Targeted Agentsmentioning

confidence: 99%

Section: Molecularly Targeted Agentsmentioning

confidence: 99%

Section: Molecularly Targeted Agentsmentioning

confidence: 99%

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PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies

2022

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“…Patients with platinum-resistant ovarian cancer have tried a variety of therapeutic regimens, including nonplatinum-based therapy, to prolong PFI and multiple drug combinations ( 39 ). The Best Approach in Recurrent-Ovarian-Cancer-with Cediranib-Olaparib (BAROCCO) trial showed that the combination of cediranib–olaparib did not significantly improve PFS in platinum-resistant patients compared with paclitaxel ( 40 ). Nonetheless, a few studies indicated that the underlying mechanisms about the initiation and progression of platinum-resistant in ovarian cancer patients.…”

Section: Discussionmentioning

confidence: 99%

MiR-320b and miR-320d as Biomarkers to Predict and Participate in the Formation of Platinum Resistance in Ovarian Cancer Patients

et al. 2022

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Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence in situ hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients.

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“…The latest randomized phase II trial compared PFS in weekly paclitaxel vs. cediranib-olaparib in platinum-resistant ovarian cancer. The results demonstrated that cediranib-olaparib oral doublet was active and might offer a nonchemotherapy option in these population, though combination of cediranib-olaparib was not superior to chemotherapy in PFS [ 121 ]. A phase II trial NSGO-AVANOVA2/ENGOT-ov24 investigated niraparib plus bevacizumab for platinum-sensitive recurrent ovarian cancer [ 122 ].…”

Section: Future Development Of Anti-angiogenic Agentsmentioning

confidence: 99%

Antiangiogenic Strategies in Epithelial Ovarian Cancer: Mechanism, Resistance, and Combination Therapy

Jin

Yuan

et al. 2022

Journal of Oncology

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Angiogenesis is one of the hallmarks of cancer and plays a crucial role in carcinogenesis and progression of epithelial ovarian cancer. Antiangiogenic agent is the first approved targeted agent in ovarian cancer. Anti-angiogenic agents mainly include agents target VEGF/VEGFR pathway, such as bevacizumab and agents target receptor tyrosine kinase, and non-VEGF/VEGFR targets of angiogenesis. Antiangiogenic agents demonstrate certain effects in ovarian cancer treatment either as monotherapy or combined with chemotherapy. Unfortunately, antiangiogenic agents, such as bevacizumab, integrated into the ovarian cancer treatment paradigm do not increase cures. Thus, the benefits of anti-angiogenic agents must be carefully weighed against the cost and associated toxicities. Antiangiogenic agents drug resistance and short of predictive biomarkers are main obstacles in ovarian cancer treatment. A combination of poly (ADP-ribose) polymerase inhibitors or immune checkpoint inhibitors might be great strategies to overcome resistance as well as enhance anti-tumor activity of anti-angiogenic drugs. Predictive biomarkers of antiangiogenic agents are in urgent need.

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Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer

Cited by 36 publications

References 18 publications

PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies

PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies

MiR-320b and miR-320d as Biomarkers to Predict and Participate in the Formation of Platinum Resistance in Ovarian Cancer Patients

Antiangiogenic Strategies in Epithelial Ovarian Cancer: Mechanism, Resistance, and Combination Therapy

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