Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

Bois, Andreas du; Floquet, Anne; Kim, Jae Weon; Rau, Joern; Campo, J. M. Del; Friedlander, Michael; Pignata, Sandro; Fujiwara, Keiichi; Vergote, Ignace; Colombo, Nicoletta; Mirza, Mansoor Raza; Monk, Bradley J.; Kimmig, Rainer; Ray‐Coquard, Isabelle; Zang, Rongyu; Díaz-Padilla, Iván; Baumann, Klaus; Mouret-Reynier, Marie Ange; Kim, Jae Hoon; Kurzeder, Christian; Lesoin, A.; Vasey, P.; Marth, Christian; Canzler, Ulrich; Scambia, Giovanni; Shimada, Muneaki; Calvert, Paula; Pujade-Lauraine, Éric; Kim, Byoung Gie; Herzog, Thomas J.; Mitrica, Ionel; Schade‐Brittinger, Carmen; Wang, Qiong; Crescenzo, Rocco J.; Harter, Philipp

doi:10.1200/jco.2014.55.7348

Cited by 299 publications

(216 citation statements)

References 25 publications

(6 reference statements)

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“…However, it has proven exceptionally difficult to show a statistically significant prolongation of OS with the addition of targeted therapy to standard treatments in patients with ovarian cancer [10][11][12][13][14][15][16][17][18][26][27][28]. Potential confounding factors for OS include the long postprogression survival period, the administration of multiple postprogression therapies, and the potential for postprogression crossover [27,29].…”

Section: Discussionmentioning

confidence: 99%

“…Evidence suggests that the Ang2 pathway plays a role in the pathophysiology of ovarian cancer [6][7][8] and upregulation of Ang2 is correlated with poor prognosis in women with recurrent ovarian cancer [9]. Several antiangiogenic agents that target the VEGF pathway have been shown to improve progression-free survival (PFS) in patients with ovarian cancer; however, a statistically significant improvement in OS has not been demonstrated [10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Monk

Poveda

Vergote

et al. 2016

Gynecologic Oncology

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• Trebananib did not improve overall survival in the intent-to-treat population.• Trebananib improved overall survival in patients with baseline ascites.• Trebananib prolonged time to second disease progression. Purpose. Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). Patients and methods. Women with recurrent disease (platinum-free interval b 12 months) were randomized to receive intravenous paclitaxel 80 mg/m 2 (3 weeks on/1 week off) plus intravenous trebananib 15 mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. Results. Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3 months; HR, 0.95; 95% CI, 0.81-1.11; P = 0.52) in the intent-to-treat population (n = 919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3 months; HR, 0.72; 95% CI, 0.55-0.93; P = 0.011) in patients with ascites at baseline (n = 295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9 months; HR, 0.85; 95% CI, 0.74-0.98; P = 0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. a b s t r a c t a r t i c l e i n f oConclusions. OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Monk

Poveda

Vergote

et al. 2016

Gynecologic Oncology

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“…Pazopanib has also been studied for use in maintenance therapy, resulting in an increase in PFS, but no improvement in overall survival (156). Pazopanib is also associated with a significant toxicity profile such as fatigue, gastrointestinal toxicities (such as nausea and/or diarrhoea), hypertension and myelosuppression (156).…”

Section: [H1]managementmentioning

confidence: 99%

“…Pazopanib is also associated with a significant toxicity profile such as fatigue, gastrointestinal toxicities (such as nausea and/or diarrhoea), hypertension and myelosuppression (156).…”

Section: [H1]managementmentioning

confidence: 99%

Ovarian cancer

Matulonis

Sood

Fallowfield

et al. 2016

Nat Rev Dis Primers

817

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Ovarian cancer is not a single disease and can be subdivided into at least five different 2 histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at late stage, and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents, and poly (ADP ribose) polymerase (PARP) inhibitors are used and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and is typically very responsive to platinum-based chemotherapy at diagnosis. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy.Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Significant progress has been made in identifying genes associated with high risk of ovarian cancer (such as BRCA1 and BRCA2) as well as a precursor lesion of HGSC called a serous tubal intraepithelial carcinoma, which hold promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. Competing interestsU.A.M. has served as a consultant for AstraZeneca, ImmunoGen, Pfizer, Genentech, and Merck.

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“…The GOG218 and ICON7 studies showed that progression-free survival (PFS) was significantly extended, but there were no significant differences in overall survival (OS). 19,20 Other drugs that have been clinically applied are the multi-targeted tyrosine kinase inhibitor pazopanib, 21 the mammalian target of rapamycin (mTOR) inhibitor temsirolimus, 22 and the angiopoietin inhibitor trebananib. 23 Although these molecularly targeted drugs are effective at extending PFS, no studies have indicated that they significantly extend OS.…”

Section: Ismail Et Al Reported That Mouse Cancer Cells In Which Cbr1mentioning

confidence: 99%

Gene therapy for ovarian cancer using carbonyl reductase 1 DNA with a polyamidoamine dendrimer in mouse models

et al. 2015

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Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

Cited by 299 publications

References 25 publications

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Ovarian cancer

Gene therapy for ovarian cancer using carbonyl reductase 1 DNA with a polyamidoamine dendrimer in mouse models

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