Association Between Tumor Egfr and Kras Mutation Status and Clinical Outcomes in Nsclc Patients Randomized to Sorafenib Plus Best Supportive Care (BSC) or Bsc Alone: Subanalysis of the Phase III Mission Trial

Mok, Tony; Paz‐Ares, Luis; Wu, Yi‐Long; Novello, Silvia; Juhász, Erzsébet; Aren, Osvaldo Rudy; Sun, Yue; Hirsh, V.; Smit, Ellen; Lathia, Chetan; Ong, Teng Jin; Peña, Carol; Pivot, Xavier; Romieu, Gilles; Bonnefoi, Hervé; Pierga, J-Y; Kerbrat, Pierre; Guastalla, J P; Lortholary, Alain; Espié, Marc; Fumoleau, P.; Serin, D.; Jacquin, J-P; Jouannaud, Christelle; Rios, M.; Abadie‐Lacourtoisie, Sophie; Tubiana-Mathieu, Nicole; Cany, Laurent; Catala, Stéphanie; Khayat, David; Pauporté, Iris; Kramar, Amanda; Goldhirsch, Aron; Piccart, Martine; Procter, Marion; Azambuja, Evandro de; Weber, Harry M.; Untch, Michael; Smith, I. 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doi:10.1093/annonc/mds499

Cited by 23 publications

(26 citation statements)

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“…Addition of axitinib resulted in numerically higher ORR, but did not improve PFS or OS compared with chemotherapy alone. However, it remains to be seen if certain subsets of patients may derive some benefits from the use of TKIs, including axitinib, as reported for other TKIs in patients with genomic abnormalities such as EGFR mutations [ 25 - 27 ], crizotinib in ALK-positive NSCLC [ 28 ], or in preclinical studies involving RET proto-oncogene rearrangements [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer

et al. 2014

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BackgroundThe efficacy and safety of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non–small-cell lung cancer (NSCLC).MethodsOverall, 170 patients were randomly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of up to six 21-day cycles (arm I); axitinib on days 2 through 19 of each cycle plus pemetrexed/cisplatin (arm II); or pemetrexed/cisplatin alone (arm III). The primary endpoint was progression-free survival (PFS).ResultsMedian PFS was 8.0, 7.9, and 7.1 months in arms I, II, and III, respectively (hazard ratio: arms I vs. III, 0.89 [P = 0.36] and arms II vs. III, 1.02 [P = 0.54]). Median overall survival was 17.0 months (arm I), 14.7 months (arm II), and 15.9 months (arm III). Objective response rates (ORRs) for axitinib-containing arms were 45.5% (arm I) and 39.7% (arm II) compared with 26.3% for pemetrexed/cisplatin alone (arm III). Gastrointestinal disorders and fatigue were frequently reported across all treatment arms. The most common all-causality grade ≥3 adverse events were hypertension in axitinib-containing arms (20% and 17%, arms I and II, respectively) and fatigue with pemetrexed/cisplatin alone (16%).ConclusionAxitinib in combination with pemetrexed/cisplatin was generally well tolerated. Axitinib combinations resulted in non-significant differences in PFS and numerically higher ORR compared with chemotherapy alone in advanced NSCLC.Trial registrationClinicalTrials.gov: NCT00768755 (October 7, 2008).

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Section: Discussionmentioning

confidence: 99%

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer

et al. 2014

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“…Mabuchi et al also showed that the continuous administration of bevacizumab could significantly prolong survival in vivo [147]. Recent results established the role of Bevacizumab in ovarian cancer, showing that it increases the efficacy of chemotherapy in the initial management of the disease [27,148] but also in relapsed platinum-sensitive [29] and platinum-resistant [149] disease.…”

Section: Targeting the Angiogenesis Related Pathways For Ovarian Cmentioning

confidence: 99%

Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

Gavalas

Liontos

Trachana

et al. 2013

IJMS

120

108

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Ovarian Cancer represents the most fatal type of gynecological malignancies. A number of processes are involved in the pathogenesis of ovarian cancer, especially within the tumor microenvironment. Angiogenesis represents a hallmark phenomenon in cancer, and it is responsible for tumor spread and metastasis in ovarian cancer, among other tumor types, as it leads to new blood vessel formation. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Growth factors have been identified to play key roles in driving angiogenesis and, thus, the formation of new blood vessels that assist in “feeding” cancer. Such molecules include the vascular endothelial growth factor (VEGF), the platelet derived growth factor (PDGF), the fibroblast growth factor (FGF), and the angiopoietin/Tie2 receptor complex. These proteins are key players in complex molecular pathways within the tumor cell and they have been in the spotlight of the development of anti-angiogenic molecules that may act as stand-alone therapeutics, or in concert with standard treatment regimes such as chemotherapy. The pathways involved in angiogenesis and molecules that have been developed in order to combat angiogenesis are described in this paper.

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“…Early data in eight vemurafenib-naïve patients showed tumour reduction but safety rather than efficacy was the purpose of this study and further research on efficacy is warranted. Two dose levels were selected for phase III investigation [149].…”

Section: Combination Of Braf and Mek Inhibitorsmentioning

confidence: 99%

Untitled

2014

Oncotarget

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As the increased knowledge of tumour heterogeneity and genetic alterations progresses, it exemplifies the need for further personalized medicine in modern cancer management. Here, the similarities but also the differential effects of RAS and BRAF oncogenic signalling are examined and further implications in personalized cancer diagnosis and therapy are discussed. Redundant mechanisms mediated by the two oncogenes as well as differential regulation of signalling pathways and gene expression by RAS as compared to BRAF are addressed. The implications of RAS vs BRAF differential functions, in relevant tumour types including colorectal cancer, melanoma, lung cancer are discussed. Current therapeutic findings and future viewpoints concerning the exploitation of RAS-BRAF-pathway alterations for the development of novel therapeutics and efficient rational combinations, as well as companion tests for relevant markers of response will be evaluated. The concept that drug-resistant cells may also display drug dependency, such that altered dosing may prevent the emergence of lethal drug resistance posed a major therapy hindrance.

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Association Between Tumor Egfr and Kras Mutation Status and Clinical Outcomes in Nsclc Patients Randomized to Sorafenib Plus Best Supportive Care (BSC) or Bsc Alone: Subanalysis of the Phase III Mission Trial

Cited by 23 publications

References 0 publications

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer

Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer

Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

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