Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial.

Rini, Brian I.; Escudier, Bernard; Tomczak, Piotr; Каприн, А. Д.; Hutson, Thomas E.; Szczylik, Cezary; Tarazi, Jamal; Rosbrook, Brad; Kim, S.; Motzer, Robert J.

doi:10.1200/jco.2011.29.15_suppl.4503

Cited by 57 publications

(55 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Currently no data from randomized clinical trials directly compare the activity and toxicity profile of various multitargeted agents. Two phase III studies comparing sunitinib with pazopanib (COMPARZ:NCT00720941) and axitinib with sorafenib, respectively, are ongoing; early results are expected by 2011 (74). Increased understanding of the pathogenesis of sunitinib-associated side effects may allow rational administration to patients.…”

Section: Discussionmentioning

confidence: 99%

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Aparicio-Gallego

Blanco

Figueroa

et al. 2011

Molecular Cancer Therapeutics

106

View full text Add to dashboard Cite

The introduction of targeted therapy represents a major advance in the treatment of tumor progression. Targeted agents are a novel therapeutic approach developed to disrupt different cellular signaling pathways. The tyrosine kinase inhibitor sunitinib specifically blocks multiple tyrosine kinase receptors that are involved in the progression of many tumors. Sunitinib is the current standard of care in first-line treatment of advanced renal cell carcinoma, and it is approved in imatinib-intolerant and imatinib-refractory gastrointestinal stromal tumors. However, it is increasingly evident that sunitinib may display collateral effects on other proteins beyond its main target receptors, eliciting undesirable and unexpected adverse events. A better understanding of the molecular mechanisms underlying these undesirable sunitinib-associated side effects will help physicians to maximize efficacy of sunitinib and minimize adverse events. Here, we focus on new insights into molecular mechanisms that may mediate sunitinib-associated adverse events. Mol Cancer Ther; 10(12); 2215-23. Ó2011 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Aparicio-Gallego

Blanco

Figueroa

et al. 2011

Molecular Cancer Therapeutics

106

View full text Add to dashboard Cite

show abstract

“…Axitinib has shown single-agent activity in several malignancies characterized by high levels of angiogenesis, including metastatic renal cell carcinoma and advanced thyroid cancer, with ORRs ranging from 30% to 44% (28,29). Recently, a phase III study evaluating axitinib in comparison to sorafenib in patients with cytokine-or tyrosine kinase inhibitor-refractory renal cell carcinoma (NCT00678392; AXIS trial) showed an improvement in PFS for patients treated with axitinib (33). We investigated the tolerability and efficacy of axitinib in a multicenter, phase II, single-arm study in patients with metastatic melanoma.…”

Section: Introductionmentioning

confidence: 99%

Multicenter, Phase II Study of Axitinib, a Selective Second-Generation Inhibitor of Vascular Endothelial Growth Factor Receptors 1, 2, and 3, in Patients with Metastatic Melanoma

Fruehauf

Lutzky

McDermott

et al. 2011

Clinical Cancer Research

102

View full text Add to dashboard Cite

Purpose: This multicenter, open-label, phase II study evaluated the safety and clinical activity of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2, and 3, in patients with metastatic melanoma.Experimental Design: Thirty-two patients with a maximum of one prior systemic therapy received axitinib at a starting dose of 5 mg twice daily. The primary endpoint was objective response rate.Results: Objective response rate was 18.8% [95% confidence interval (CI), 7.2-36.4], comprising one complete and five partial responses with a median response duration of 5.9 months (95% CI, 5.0-17.0). Stable disease at 16 weeks was noted in six patients (18.8%), with an overall clinical benefit rate of 37.5%. Six-month progression-free survival rate was 33.9%, 1-year overall survival rate was 28.1%, and median overall survival was 6.6 months (95% CI, 5.2-9.0). The most frequently (>15%) reported nonhematologic, treatment-related adverse events were fatigue, hypertension, hoarseness, and diarrhea. Treatment-related fatal bowel perforation, a known class effect, occurred in one patient. Axitinib selectively decreased plasma concentrations of soluble VEGFR (sVEGFR)-2 and sVEGFR-3 compared with soluble stem cell factor receptor (sKIT). No significant association was noted between plasma levels of axitinib and response. However, post hoc analyses indicated potential relationships between efficacy endpoints and diastolic blood pressure of 90 mm Hg or higher as well as baseline serum lactate dehydrogenase levels.Conclusions: Axitinib was well tolerated, showed a selective VEGFR-inhibitory profile, and showed single-agent activity in metastatic melanoma. Further evaluations of axitinib, alone and combined with chemotherapy, are ongoing. Clin Cancer Res; 17(23); 7462-9. Ó2011 AACR.

show abstract

“…Acquired resistance to anti-VEGF therapy may mean that the order in which targeted agents are introduced to patients is important, such that a survival benefit may be derived from sequential monotherapy with multitargeted TKIs (16). An analysis of a prospective trial (17), numerous retrospective studies, and a subgroup analysis of expanded-access programs for sorafenib suggested that there is an increase in PFS for a TKI switch in mRCC (18).…”

Section: Introductionmentioning

confidence: 99%

Combining Antiangiogenics to Overcome Resistance: Rationale and Clinical Experience

Moreno

Basu

Molife

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Antiangiogenic therapies are now well established in oncology clinical practice; however, despite initial optimism, the results of late-phase trials, especially in the adjuvant setting, have largely proved disappointing. In the context of metastatic disease, resistance to antiangiogenic agents arises through a range of mechanisms, including the development of alternative angiogenic pathways. One of the proposed strategies to overcome this resistance is to combine antiangiogenic agents with different mechanisms of action. Earlyphase clinical trials assessing the tolerability and efficacy of different combinations of antiangiogenic drugs, including those that target the VEGF pathway or the angiopoietins, as well as vascular disrupting agents, are increasing in number. An example of this strategy is the combination of sorafenib and bevacizumab, which has elicited major responses in different tumor types, including ovarian carcinoma and glioblastoma. However, overlapping and cumulative toxicities pose a real challenge. This review summarizes the preclinical rationale for this approach and current clinical experience in combining antiangiogenic therapies.

show abstract

Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial.

Cited by 57 publications

References 0 publications

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Multicenter, Phase II Study of Axitinib, a Selective Second-Generation Inhibitor of Vascular Endothelial Growth Factor Receptors 1, 2, and 3, in Patients with Metastatic Melanoma

Combining Antiangiogenics to Overcome Resistance: Rationale and Clinical Experience

Contact Info

Product

Resources

About