SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma: trial

SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma

Population

Previously untreated metastatic renal cell carcinoma (the 2009 report states clear cell histology)

Design

Multicentre randomised phase 3 trial of sunitinib 50 mg orally once daily for 4 weeks followed by 2 weeks off, in repeated 6-week cycles, versus interferon alfa 9 MU subcutaneously three times weekly. Primary end point progression-free survival; secondary end points included objective response rate, overall survival, patient-reported outcomes and safety. Overall survival and updated results were reported in the Journal of Clinical Oncology in 2009.

Primary endpoint

PFS

Arms

Sunitinib (experimental, n = 375): Sunitinib 50 mg orally once daily, 4 weeks on and 2 weeks off, in 6-week cycles
Interferon alfa (control, n = 375): Interferon alfa 9 MU subcutaneously three times weekly

People

Motzer RJ, senior author Figlin RA

PFSHR 0.42 (95% CI 0.32–0.54)Δ median PFS+6 monthsΔ ORR+25 pointsOSHR 0.821 (95% CI 0.673–1.001)Δ median OS+4.6 monthsΔ ORR+35 points

Show the numbers

Results reported for SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma
Endpoint	Analysis	Sunitinib	Interferon alfa	Effect
PFSRandomised patients as described in the abstract (analysis population not stated there)	primaryMotzer 2007	median 11 months	median 5 months	HR 0.42 (95% CI 0.32–0.54)P<0.001Medians are rounded to whole months in the abstract.
ORRRandomised patients as described in the abstract (analysis population not stated there)	primaryMotzer 2007	31%	6%	P<0.001
OSITT (all randomised patients, per the JCO 2009 full text)	finalMotzer 2009	median 26.4 months	median 21.8 months	HR 0.821 (95% CI 0.673–1.001)P=0.051Primary analysis by unstratified log-rank test (P=0.051); the unstratified Wilcoxon test gave P=0.013. The stratified log-rank hazard ratio was 0.818 (95% CI 0.669 to 0.999; P=0.049). After stopping trial treatment 33% of the interferon alfa group received sunitinib and 32% received other VEGF-signalling inhibitors.
ORRRandomised patients (375 per arm); investigator-assessed response (central imaging review had been discontinued in September 2007)	long term-updateMotzer 2009	47%	12%	P<0.001Updated follow-up with investigator-assessed response; not comparable with the 31% versus 6% of the primary report.

Results reported for SU011248 Versus Interferon-Alfa As First-Line Systemic Therapy For Patients With Metastatic Renal Cell Carcinoma
Endpoint	Analysis	Sunitinib	Interferon alfa	Effect
PFSRandomised patients as described in the abstract (analysis population not stated there)	primaryMotzer 2007	median 11 months	median 5 months	HR 0.42 (95% CI 0.32–0.54)P<0.001Medians are rounded to whole months in the abstract.
ORRRandomised patients as described in the abstract (analysis population not stated there)	primaryMotzer 2007	31%	6%	P<0.001
OSITT (all randomised patients, per the JCO 2009 full text)	finalMotzer 2009	median 26.4 months	median 21.8 months	HR 0.821 (95% CI 0.673–1.001)P=0.051Primary analysis by unstratified log-rank test (P=0.051); the unstratified Wilcoxon test gave P=0.013. The stratified log-rank hazard ratio was 0.818 (95% CI 0.669 to 0.999; P=0.049). After stopping trial treatment 33% of the interferon alfa group received sunitinib and 32% received other VEGF-signalling inhibitors.
ORRRandomised patients (375 per arm); investigator-assessed response (central imaging review had been discontinued in September 2007)	long term-updateMotzer 2009	47%	12%	P<0.001Updated follow-up with investigator-assessed response; not comparable with the 31% versus 6% of the primary report.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.42	0.32–0.54
OS	0.821	0.673–1.001

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Sunitinib (experimental)
Interferon alfa (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Sunitinib	Interferon alfa
0	100.0%	100.0%
7	64.3%	37.9%
14	41.4%	14.4%
21	26.6%	5.4%
28	17.1%	2.1%

Illustrative — modelled from reported values, not trial data. OS, final.

Show curves

Sunitinib (experimental)
Interferon alfa (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Sunitinib	Interferon alfa
0	100.0%	100.0%
17	64.0%	58.2%
33	42.0%	35.0%
50	26.9%	20.4%
66	17.7%	12.3%

Appears in

2006 Sunitinib versus interferon alfa as first-line therapy (2006-2007)

Sources

Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115-24.
PubMed DOI
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(22):3584-90.
PubMed DOI