Beyond the Abstract - Overall survival and updated results from a phase II study of sunitinib in Japanese patients with metastatic renal cell carcinoma, by Hideyuki Akaza, MD

BERKELEY, CA ( - Sunitinib is an oral, multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR-1, -2 and -3) and platelet-derived growth factor receptors (PDGFR-α and –β), approved multinationally for the treatment of first- and second-line advanced renal cell carcinoma (RCC).1

Interim results from the first Japanese phase II study of single-agent sunitinib in metastatic RCC were reported in March 2010.2 The primary study endpoint of objective response rate (ORR) was 48.0% in treatment-naïve patients, 46.2% in pretreated patients and 47.1% in the overall intent-to-treat (ITT) population. Median progression-free survival (PFS) was 10.6, 7.8 and 10.6 months, respectively. Based on these results, sunitinib is now also approved in Japan for patients with RCC not indicated for curative resection and patients with metastatic RCC. Since median overall survival (OS) had not yet been reached at the time of interim analysis of this study, we subsequently reported the final OS analysis along with updated efficacy and safety findings.

Fifty-one Japanese patients with RCC with a clear-cell component and metastases (25 treatment-naïve and 26 cytokine-refractory patients) received sunitinib 50 mg/day in repeated 6-week cycles (4 weeks on treatment followed by 2 weeks off; Schedule 4/2) until disease progression, requirement for additional anticancer therapy, development of left ventricular systolic dysfunction or withdrawal of consent. First-line and pretreated patients received a median 6.0 and 9.5 treatment cycles, respectively.

At the end of the study, investigator-assessed ORR was 52.0%, 53.8% and 52.9% in the first-line, pretreated and overall ITT populations, respectively. Final results for median PFS were 12.2 and 10.6 months in first-line and pretreated patients, respectively. Fourteen patients in each arm died (56% and 54%, respectively), and median OS was 33.1 and 32.5 months for the first-line and pretreated groups, respectively.

In all patients, most adverse events (AEs) were mild to moderate (Grades 1 or 2) in severity. Commonly reported Grade 3 treatment-related AEs in the first-line and pretreated groups, respectively, included: diarrhea (16% and 15%), fatigue (16% and 27%), hand–foot syndrome (16% and 19%) and hypertension (12% and 19%). In total, three Grade 4 treatment-related AEs were reported (hypomagnesemia, dyspnea and fatigue; all n=1). No Grade 5 treatment-related AEs were reported. Laboratory abnormalities were reported frequently in both patient populations, including Grade 3 or 4 decreased platelet count (56% and 54% in the first-line and pretreated populations, respectively), decreased neutrophil count (44% and 62%), and increased lipase (32% and 65%). Forty-six patients (90%) required dose reduction or temporary discontinuation, and 13 patients (25%) discontinued, due to treatment-related AEs.

In Japanese patients with first-line or cytokine-refractory metastatic RCC and Eastern Cooperative Oncology Group performance status of 0 or 1, sunitinib 50 mg/day administered on Schedule 4/2 showed significant antitumor activity (including a median OS benefit exceeding 2.5 years and a final ORR >50%) and was generally well tolerated. Due to potential differences in the clinical backgrounds of each patient population, the results do not indicate whether sunitinib should be used in treatment-naïve or cytokine-pretreated patients. Safety and efficacy observations in this study were generally similar to those in Western studies,3–5 although there was a trend towards greater efficacy and an increased incidence of hematologic AEs in Japanese patients. At the present time, it is not clear why such differences may exist.

As the first Japanese phase II study of single-agent sunitinib in both treatment-naïve and cytokine-pretreated patients with metastatic RCC, this trial and its publication fulfilled an unmet need in the literature regarding the use of sunitinib in Asian patients. In addition, these robust findings provide additional support for the proven efficacy demonstrated in Western studies. They also complement previously published population-pharmacokinetic (PK) modeling data for sunitinib in which Japanese patients were found to have a similar PK profile to Caucasian patients, leading those authors to conclude (in part) that no adjustments to the sunitinib starting dose are recommended based on Asian race.6


Medical writing support was provided by Andy Gannon at ACUMED® (Tytherington, UK) with funding from Pfizer Inc.



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  3. Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006;295:2516–2524.
  4. Motzer RJ, Michaelson MD, Rosenberg J, Bukowski RM, Curti BD, George DJ, et al. Sunitinib efficacy against advanced renal cell carcinoma. J Urol 2007;178:1883–1887.
  5. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27:3584–3590.
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Hideyuki Akaza, MD as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.


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