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Overall Survival with Sunitinib vs. Interferon for

Metastatic Renal Cell CarcinomaAUTHORS: RA Figlin, TE Hutson, P Tomczak, MD Michaelson, RM Bukowski,

S Negrier, X Huang, ST Kim, I Chen, RJ MotzerASCO 2008 Abs 5024

Reviewers: Drs. Daniel Heng and Lori Wood

Date posted: June 18/2008

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RSunitinib 50 mg PO OD (4/2wks on/off)N=375

IFN-alfa 9 MU SC 3/wkN=375

750 patients

Treatment naive Metastatic clear-

cell renal cellcarcinoma

MSKCC Risk Profiles:Favorable 36%

Intermediate 57%Poor 7%

Prior Nephrectomy

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RESULTS

Suntinib IFN-alpha p-value

Response Rate (%) 47 12 <0.000001

Median PFS (mos)MSKCC Risk PFS (95%CI):

Favorable

Intermediate

Poor

11

14.5 (11.3-16.8)

10.6 (8.2-10.9)

3.7 (2.0-9.8)

5

7.9 (7-10.5)

3.8 (3.6-4.0)

1.2 (1.0-2.4)

<0.000001

OS

(median, mos)26.4 21.8

0.051 log rank

0.0128 wilcoxon

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Final Overall Survival Data

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STUDY COMMENTARY

•59% of patients in the interferon group had second-line treatment including:

•33% with sunitinib, 32% with another VEGF inhibitor

•The traditional gold standard Log rank p value weights all patient events and time points equally throughout the study. p=0.051.

•The secondary prespecified Wilcoxon p value places more weight on early rather than later patient events and time points. p=0.0128.

•Calculating the p value while censoring patients with second-line treatment produced significant results but this introduced bias as there likely was a systematic difference in patients that were censored.

•Poor risk patients only accounted for 7% of the patients. Thus, the subset analysis may not be powered sufficiently to detect a difference and the generalizability of these results to this subset may be limited.

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

•Sunitinib produces a progression free survival benefit compared to IFN alpha in patients with mRCC treated first-line. PFS was the primary endpoint and this is a positive study.

•There is a borderline overall survival benefit but this endpoint is clouded by second-line treatment of IFN patients with targeted agents. This may dilute the true OS benefit

•Sunitinib remains a standard of care for the first-line treatment of mRCC in Canada

•As of June 2008 in Canada:

•Some provincial cancer programs cover the cost of sunitinib

•Several private Canadian insurance plans include sunitinib

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Treatment of mRCC:Current Status

Setting Patients Therapy

(level 1 evidence)

Other Alternatives

Untreated Good or intermediate risk

Sunitinib

Bevacizumab* + IFN

HD IL-2

Sorafenib

Clinical Trial

Observation

Poor risk Temsirolimus Sunitinib

Clinical Trial

Second-line Cytokine refractory Sorafenib Sunitinib, Bevacizumab* + IFN

Prior VEGF (or mTOR)

Everolimus*

Clinical Trial

Targeted therapy not previously used

*Bevacizumab and Everolimus are not yet FDA or Health Canada Approved for RCC

Adapted with permission from Dr. Brian Rini