Axitinib Versus Sorafenib in First-Line Metastatic Renal Cell Carcinoma: Overall Survival From a Randomized Phase III Trial

Hutson, Thomas E.; Al-Shukri, Salman Hasunovich; Stus, V.P.; Lipatov, Oleg; Shparyk, Yaroslav; Bair, Angel H.; Rosbrook, Brad; Andrews, Glen; Vogelzang, Nicholas J.

doi:10.1016/j.clgc.2016.05.008

Cited by 57 publications

(45 citation statements)

References 11 publications

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“…The results of the trial were presented at first data cutoff; axitinib versus sorafenib yielded numerically (but not statistically) longer median PFS (10.1 vs 6.5 months, respectively; HR, 0.77; 95% CI, 0.56 [one‐sided]; P = .038) and higher response rates (32% vs 15%, respectively; P < .001) . The updated OS results were published more recently and showed no difference between the 2 groups (27.1 vs 23.3 months, respectively; HR, 0.99; 95% CI, 0.73 [one‐sided]; P = .49) …”

Section: Systemic Therapy For Metastatic Diseasementioning

confidence: 99%

Treatment of renal cell carcinoma: Current status and future directions

Barata

Rini

2017

CA A Cancer J Clinicians

664

528

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Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society.

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Section: Systemic Therapy For Metastatic Diseasementioning

confidence: 99%

Treatment of renal cell carcinoma: Current status and future directions

Barata

Rini

2017

CA A Cancer J Clinicians

664

528

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“…In treatment‐naïve patients with metastatic RCC in a randomized open‐label phase III trial, the difference in median PFS between axitinib and sorafenib did not reach significance and no survival advantage was observed with axitinib over sorafenib . However, axitinib showed antitumor activity with an acceptable safety profile.…”

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confidence: 98%

Overall survival of first‐line axitinib in metastatic renal cell carcinoma: Japanese subgroup analysis from phase II study

et al. 2017

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Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression‐free survival of 27.6 months in treatment‐naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and safety in 44 Japanese patients and compared the results with 169 non‐Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first‐line metastatic RCC were explored in all patients using a Cox proportional hazard model. With median follow‐up of 33 months, fewer than half (16 of 44) of the Japanese patients had died and median OS was not reached (95% confidence interval [CI], 38.8 months–not estimable), whereas 107 of 169 (63%) non‐Japanese patients had died and median OS was 33.9 months (95% CI, 28.9–42.7). Estimated 1‐year, 2‐year and 3‐year survival probability (95% CI) was 86.4% (76.2–96.5), 75.0% (62.2–87.8) and 68.2% (54.4–81.9), respectively, in Japanese patients, and was higher than that in non‐Japanese patients (75.1% [68.4–81.8], 62.1% [54.5–69.7] and 47.2% [39.3–55.1], respectively). The updated safety analysis did not reveal any new adverse events of concern among Japanese or non‐Japanese patients. The multivariate analysis identified that lower baseline Eastern Cooperative Oncology Group performance status, lower baseline tumor burden, and longer time from histopathological diagnosis to treatment were significant positive predictors of OS. The current analysis confirmed the clinical activity of axitinib in treatment‐naïve Japanese patients with metastatic RCC, with an acceptable toxicity profile.

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“…The drug is approved in Europe, the United States, Japan, and elsewhere for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy, and is currently a preferred choice as second‐line therapy for patients progressing after first‐line therapy . Moreover, axitinib has shown clinical activity in first‐line mRCC in recent phase II and III trials . Axitinib is approved at a starting dose of 5 mg twice daily (b.i.d.)…”

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confidence: 99%

A Pharmacometric Framework for Axitinib Exposure, Efficacy, and Safety in Metastatic Renal Cell Carcinoma Patients

Schindler

Amantea

Karlsson

et al. 2017

CPT Pharmacometrics Syst. Pharmacol.

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The relationships between exposure, biomarkers (vascular endothelial growth factor (VEGF), soluble VEGF receptors (sVEGFR)‐1, ‐2, ‐3, and soluble stem cell factor receptor (sKIT)), tumor sum of longest diameters (SLD), diastolic blood pressure (dBP), and overall survival (OS) were investigated in a modeling framework. The dataset included 64 metastatic renal cell carcinoma patients (mRCC) treated with oral axitinib. Biomarker timecourses were described by indirect response (IDR) models where axitinib inhibits sVEGFR‐1, ‐2, and ‐3 production, and VEGF degradation. No effect was identified on sKIT. A tumor model using sVEGFR‐3 dynamics as driver predicted SLD data well. An IDR model, with axitinib exposure stimulating the response, characterized dBP increase. In a time‐to‐event model the SLD timecourse predicted OS better than exposure, biomarker‐ or dBP‐related metrics. This type of framework can be used to relate pharmacokinetics, efficacy, and safety to long‐term clinical outcome in mRCC patients treated with VEGFR inhibitors. (ClinicalTrial.gov identifier NCT00569946.)

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Axitinib Versus Sorafenib in First-Line Metastatic Renal Cell Carcinoma: Overall Survival From a Randomized Phase III Trial

Cited by 57 publications

References 11 publications

Treatment of renal cell carcinoma: Current status and future directions

Treatment of renal cell carcinoma: Current status and future directions

Overall survival of first‐line axitinib in metastatic renal cell carcinoma: Japanese subgroup analysis from phase II study

A Pharmacometric Framework for Axitinib Exposure, Efficacy, and Safety in Metastatic Renal Cell Carcinoma Patients

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