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CCO > Oncology > Conference Coverage > Clin Onc June 2011 > Genitourinary Cancers > *Capsule Summary* Saturday, May 05, 2012 Email a Colleague Print this page Capsule Summary *CCO Independent Conference Coverage* of the 2011 American Society of Clinical Oncology Annual Meeting* *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. AXIS: Axitinib Shows Significant PFS Improvement vs Sorafenib in Refractory Metastatic RCC Posting Date: June 08, 2011 * AXIS: randomized phase III trial^[1] Summary of Key Conclusions * Axitinib prolonged PFS vs sorafenib in patients with treatment-refractory metastatic renal cell carcinoma (RCC) o Risk of progression reduced by 33% with axitinib * Tolerability profiles generally similar with axitinib and sorafenib o More hypertension and hypothyroidism with axitinib vs sorafenib but less hand-foot syndrome, rash, and alopecia * Authors suggest these data support axitinib as the standard second-line therapy for advanced RCC Background * Standard of care in patients with treatment-refractory metastatic RCC not well defined o No targeted therapies compared in randomized trial to date * Axitinib, an oral selective inhibitor of vascular endothelial growth factor receptor–1, –2, and –3^[2] * Demonstrated antitumor activity in 2 phase II trials o 44% ORR in cytokine-refractory RCC^[3] o 23% ORR in sorafenib-refractory RCC^[4] * Current study designed to compare axitinib vs sorafenib in patients with treatment-refractory metastatic RCC Schematic of Study Design Eligibility * Inclusion criteria o Metastatic RCC with clear cell histology o ECOG performance score 0-1 o Disease progression following 1 previous regimen containing sunitinib, bevacizumab plus interferon alfa, temsirolimus, or cytokines o Adequate organ function o Measurable disease by Response Evaluation Criteria in Solid Tumors Baseline Characteristics * N = 723 o Treatment history + Sunitinib: n = 389 + Cytokines: n = 251 + Temsirolimus: n = 24 + Bevacizumab: n = 59 */Characteristic/* */Axitinib (n = 361)/* */Sorafenib (n = 362)/* Median age, yrs (range) 61 (20-82) 61 (22-80) Male, % 73 71 Race, % * White 77 74 ECOG performance score, % * 0 54 55 * 1 45 44 MSKCC risk category (no. of risk factors), % * Favorable (0) 40 40 * Intermediate (1-2) 54 54 * Poor (≥ 3) 2 2 /MSKCC, Memorial Sloan-Kettering Cancer Center. / Description of Current Analysis * Primary endpoint o PFS * Secondary endpoints o OS o ORR o Safety o Duration of response o Comparison of kidney cancer–specific symptom profile with health-related quality of life + Used the Functional Assessment of Cancer Therapy Kidney Symptom Index and EuroQol 5D * Assessments o Tumor evaluation at screening, Week 6, Week 12, then every 8 weeks thereafter o In-office safety assessment at Week 2, Week 4, then every 4 weeks thereafter o Home blood pressure monitoring o Quality of life by self-report at screening, every 4 weeks, at study end, and 28 days following last dose * Statistical considerations o 1-sided log-rank test (alpha: 0.025) o Adequately powered to detect ≥ 40% improvement in median PFS o PFS assessed by blinded independent review committee (IRC) Main Findings * Axitinib significantly prolongs PFS vs sorafenib (IRC assessment) o Median PFS with axitinib: 6.7 months (95% CI: 6.3-8.6) o Median PFS with sorafenib: 4.7 months (95% CI: 4.6-5.6) + HR: 0.665 (95% CI: 0.544-0.812; /P/ < .0001) * Statistically significant PFS benefit limited to patients previously treated with cytokines or sunitinib */PFS by Previous Therapy,* Mos/* */Axitinib (n = 361)/* */Sorafenib (n = 362)/* */HR/* */P Value/* Cytokines (n = 251) 12.1 6.5 0.464 < .0001 Sunitinib (n = 389) 4.8 3.4 0.741 .011 Temsirolimus (n = 24) 10.1 5.3 0.511 .142 Bevacizumab (n = 59) 4.2 4.7 1.147 .637 *IRC assessment. * PFS benefit with axitinib in nearly all patient subgroups defined by baseline characteristics and prognostic factors o Axitinib benefit regardless of ECOG performance score (1 vs 0), race (white vs nonwhite), age (younger than 65 years vs 65 years or older), or MSKCC risk category (favorable vs intermediate/poor) o Axitinib also favored in female patients and patients based in Asia or Europe * More patients given axitinib with PR vs sorafenib (19.4% vs 9.4%, respectively) o Risk ratio for response: 2.1 (95% CI: 2.4-3.0; /P/ = .0001) Other Outcomes * Similar rate of dose modifications with axitinib vs sorafenib o 3.9% in axitinib group and 8.2% in sorafenib group discontinued due to treatment-related adverse events (AEs) * Treatment generally well tolerated with similar toxicity profiles in both groups o All-grade hypertension and hypothyroidism more common with axitinib vs sorafenib o All-grade hand-foot syndrome, rash, and alopecia less common with axitinib vs sorafenib */Grade 3/4 AE, %/* */Axitinib (n = 359)/* */Sorafenib (n = 355)/* Diarrhea 11 7 Hypertension 16 11 Fatigue 11 5 Nausea 3 1 Vomiting 3 1 Hypothyroidism < 1 0 Stomatitis 1 < 1 Hand-foot syndrome 5 16 Rash < 1 4 Alopecia 0 0 Neutropenia 1 1 Anemia < 1 4 Thrombocytopenia < 1 0 Lymphopenia 3 4 Hypophosphatemia 2 16 Hypercalcemia < 1 0 Hypocalcemia 1 1 Elevated lipase 5 15 References 1. Rini BI, Escudier B, Tomczak P, et al. Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): results of phase III AXIS trial. Program and abstracts of the 2011 American Society of Clinical Oncology Annual Meeting; June 3-7, 2011; Chicago, Illinois. Abstract 4503. 2. Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008;14:7272-7283. 3. Rixe O, Bukowski RM, Michaelson MD, et al. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007;8:975-984. 4. Rini BI, Wilding G, Hudes G, et al. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol. 2009;27:4462-4468. ©2011 Clinical Care Options, LLC. May be copied for personal use only. To request permission for other use, contact at permissions@clinicaloptions.com . Expert Analysis Expert Analysis: Genitourinary Cancers Begin the Expert Analysis Faculty: David I. Quinn, MD, PhDBrian I. Rini, MDNicholas J. Vogelzang, MD * David I. Quinn, MD, PhD * Brian I. Rini, MD * Nicholas J. Vogelzang, MD Learning Objectives Upon completion of this activity, participants should be able to: * Apply recent practice-changing findings to the treatment of patients with renal cell carcinoma, prostate cancer, and bladder to increase survival * Discuss with colleagues the potential clinical utility of circulating tumor cells as an efficacy-response biomarker in the treatment of castration-resistant prostate cancer * Apply recent clinical findings to the care of patients with metastatic castration-resistant prostate cancer * Provide appropriate care and counsel for patients and their families Topics covered include: * AXIS: Axitinib vs Sorafenib in Metastatic RCC * AXIS: Quality-of-Life Substudy * PSA Screening Based on Long-term Risk * CTCs as Prognostic Biomarker in Metastatic CRPC * Abiraterone as Palliative Agent in CRPC * Orteronel: Novel Antiandrogen in Prostate Cancer * Cabozantinib: Novel TKI in Prostate Cancer * Gem/Cis vs MVAC in Bladder Cancer * Volasertib in Urothelial Cancer CREDIT INFORMATION *Release Date:* 7/27/11 *Expiration Date:* 7/26/12 *Physicians:* maximum of 1.0 /AMA PRA Category 1 Credit/™ *Registered Nurses:* 0.9 Nursing contact hours *Status:* Click here to earn credit Related Content Read Capsule Summaries from this track: * Dose-Dense Gemcitabine/Cisplatin Shows Similar Efficacy and Improved Tolerability vs Dose-Dense MVAC in Advanced Urothelial Cancer * Three Consecutive PSA Screening Tests Can Distinguish Men Unlikely to Benefit From Further Testing * Cabozantinib Therapy Demonstrated Antitumor Activity and Bone Pain Improvement in Patients With mCRPC * Abiraterone Plus Prednisone Improves Bone-Related Symptoms Over Prednisone Alone in Patients With CRPC and Bone Metastases * TAK-700 With or Without Prednisone Induces PSA Response and Reduces Testosterone and DHEA Levels in Patients With Metastatic CRPC * Single-Agent Volasertib as Second-line Therapy for Advanced Urothelial Cancer Active and Well Tolerated in Phase II Trial * Everolimus Clinically Active in Metastatic Transitional Cell Carcinoma of the Urothelium * CTCs Significantly Associated With OS Benefit Following Abiraterone Treatment in Patients With mCRPC CCO > Oncology > Conference Coverage > Clin Onc June 2011 > Genitourinary Cancers > *Capsule Summary* Other CCO Sites: CCO Icon Home Hepatitis Hepatitis HIV HIV Oncology Oncology Urology Urology CCO Corporate Icon inPractice CCO Corporate Icon Corporate SiteMap | RSS | Contact Us | Help | Site Requirements | Terms of Use | Privacy Policy | Oncology Site Tour | International Editions ©2003-2012 Clinical Care Options, LLC. 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