ASSURE: trial | Bending the Curve: Trial by Trial

ASSURE

Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial

Phase 3N = 1,943NCT00326898

Population

Completely resected non-metastatic renal-cell carcinoma of pathological stage high-grade T1b or greater, with adequate cardiac, renal and hepatic function.

Design

Double-blind, placebo-controlled, randomised (1:1:1) phase 3 trial in 226 centres in the USA and Canada, April 2006 to September 2010. Treatment lasted 54 weeks. After high rates of toxicity-related discontinuation in the first 1323 patients, the starting dose of each drug was reduced and then titrated up. On 16 October 2014 the data safety monitoring committee recommended that blinded follow-up stop because of low conditional power for the primary endpoint.

Primary endpoint

DFS

Arms

Sunitinib (experimental, n = 647): Sunitinib 50 mg orally per day for the first 4 weeks of each 6-week cycle, 54 weeks
Sorafenib (experimental, n = 649): Sorafenib 400 mg orally twice per day, 54 weeks
Placebo (control, n = 647): Matching placebo, 54 weeks

People

Haas NB, ECOG-ACRIN Cancer Research Group

DFSHR 1.02Δ median DFS−0.8 yearsDFSHR 0.97Δ median DFS−0.5 years

Show the numbers

Results reported for ASSURE
Endpoint	Analysis	Sunitinib / Sorafenib	Placebo	Effect
DFS	primaryHaas 2016	median 5.8 years	median 6.6 years	HR 1.02P=0.8038Hazard ratio with a 97.5% confidence interval of 0.85 to 1.23 (not a 95% interval). Medians are reported with interquartile ranges, not confidence intervals. Treatment was discontinued by 193 (44%) of 438 patients on sunitinib in the first 1323 enrolled, before the dose reduction.
DFS	primaryHaas 2016	median 6.1 years	median 6.6 years	HR 0.97P=0.7184Hazard ratio with a 97.5% confidence interval of 0.80 to 1.17 (not a 95% interval). Medians are reported with interquartile ranges, not confidence intervals. Treatment was discontinued by 199 (45%) of 441 patients on sorafenib in the first 1323 enrolled, before the dose reduction.

Results reported for ASSURE
Endpoint	Analysis	Sunitinib / Sorafenib	Placebo	Effect
DFS	primaryHaas 2016	median 5.8 years	median 6.6 years	HR 1.02P=0.8038Hazard ratio with a 97.5% confidence interval of 0.85 to 1.23 (not a 95% interval). Medians are reported with interquartile ranges, not confidence intervals. Treatment was discontinued by 193 (44%) of 438 patients on sunitinib in the first 1323 enrolled, before the dose reduction.
DFS	primaryHaas 2016	median 6.1 years	median 6.6 years	HR 0.97P=0.7184Hazard ratio with a 97.5% confidence interval of 0.80 to 1.17 (not a 95% interval). Medians are reported with interquartile ranges, not confidence intervals. Treatment was discontinued by 199 (45%) of 441 patients on sorafenib in the first 1323 enrolled, before the dose reduction.

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

Show curves

Sunitinib (experimental)
Placebo (control)

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

Data table (modelled values)

Months	Sunitinib	Placebo
0	100.0%	100.0%
49	61.4%	65.1%
99	37.3%	42.0%
148	22.9%	27.4%
198	13.9%	17.7%

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

Show curves

Sorafenib (experimental)
Placebo (control)

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

Data table (modelled values)

Months	Sorafenib	Placebo
0	100.0%	100.0%
49	62.9%	65.1%
99	39.2%	42.0%
148	24.6%	27.4%
198	15.3%	17.7%

Appears in

2016 Adjuvant VEGF-TKIs: ASSURE, S-TRAC, PROTECT and SORCE

Sources

Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016;387(10032):2008-16.
PubMed DOI