A6181004

20 evidence topics · 3 sources

Objective

Anticancer activity assessment

“anticancer efficacy” (opens the source at this quote in a new tab)

Location and study date

Registry-reported study dates

Milestone	Date as recorded
Study start	“1/12/2003”
Last data collection	“1/05/2008”

Study design

Randomized and blinded comparison

“randomised, double-blind, placebo-controlled” (opens the source at this quote in a new tab)

Eligibility criteria

Minimum age

“18 Years” (opens the source at this quote in a new tab)

Prior treatment requirement

“Failed Gleevec treatment or intolerant to Gleevec therapy” (opens the source at this quote in a new tab)

Treatment

Sunitinib once-daily oral starting dose

“50 mg” (opens the source at this quote in a new tab)

Intermittent treatment schedule

“4 weeks on study drug/2 weeks off study drug.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using time to tumor progression as the primary endpoint

Primary endpoint

“time to tumour progression” (opens the source at this quote in a new tab)

Regulatory distinction between progression and progression-free survival

“TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths.” (opens the source at this quote in a new tab)
“Compared with TTP, PFS is the preferred regulatory endpoint.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized population

Population	Participants
Overall	“312”

Description of analysis sets

Reported analysis approaches

“Intention-to-treat” (opens the source at this quote in a new tab)
“modified intention-to-treat” (opens the source at this quote in a new tab)
“per-protocol” (opens the source at this quote in a new tab)

Detailed analysis-set definitions

“Analysed study populations included intention-to-treat (ITT; all patients randomised to treatment), modified ITT (all ITT patients with disease progression on imatinib confirmed by central radiology laboratory), and per-protocol (all patients who received at least one dose of assigned study treatment).” (opens the source at this quote in a new tab)
“ITT data are presented for efficacy and per-protocol data for safety; modified ITT data are discussed where relevant.” (opens the source at this quote in a new tab)

Results

Participant disposition

Summary

The trial was unblinded early after a planned interim analysis showed a longer time to progression with sunitinib.

Randomized treatment allocation

Treatment	Participants
Sunitinib	“207”
Placebo	“105”

Baseline characteristics

Balance between randomized groups and prior imatinib exposure

“Between December, 2003, and January, 2005, 312 patients were enrolled from 56 centres in 11 countries and were randomised to receive blinded sunitinib (n=207) or placebo (n=105).” (opens the source at this quote in a new tab)
“All characteristics were well balanced between the groups. The most common metastatic sites were the liver, peritoneum, and mesentery.” (opens the source at this quote in a new tab)
“The sunitinib and placebo groups were also similar in terms of median maximum dose, median daily dose (503 mg vs 485 mg), and median cumulative dose (367 400 mg vs 376 400 mg) of previous imatinib therapy, as well as in other aspects of treatment history.” (opens the source at this quote in a new tab)

Efficacy results

Time to tumor progression

Measure	Sunitinib	Placebo
Median, weeks	“27.3”	“6.4”

Treatment effect on time to progression

Measure	Value
Hazard ratio	“0.33”
P value	“p<0.0001”

Overall survival with crossover permitted

“Despite the availability of the option to cross over, overall survival obtained with initial sunitinib treatment was better that that obtained with placebo (figure 4; HR 0·49, 95% CI 0·29–0·83; p=0·007)” (opens the source at this quote in a new tab)
“the trial was unblinded early when a planned interim analysis showed significantly longer time to tumour progression with sunitinib” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Common treatment-related adverse events

“fatigue, diarrhoea, skin discolouration, and nausea.” (opens the source at this quote in a new tab)

Study limitations

Summary

The randomized trial was unblinded early after its planned interim analysis. Its primary endpoint was time to tumor progression rather than progression-free survival, which also counts deaths. The comparison was sunitinib against placebo, not bezuclastinib plus sunitinib against sunitinib.