EURURO Vol. 73 No. 1

3.2.

Subgroup analysis

The majority of subgroups selected according to baseline

characteristics experienced longer DFS on sunitinib com-

pared to placebo

( Fig.1 )

. Subgroups favoring sunitinib by HR

with an upper 95% CI boundary

1.0 included age

45 yr

(HR 0.43, 95% CI, 0.20

–

0.92) or 65 yr (HR 0.59, 95% CI 0.36

–

0.95); normal weight (HR 0.63, 95% CI 0.41

–

0.96); and ECOG

PS 0 (HR 0.69, 95% CI 0.51

–

0.93). Other groups included

Fuhrman grade 3 or 4 tumors (HR 0.73, 95% CI 0.55

–

0.98);

higher risk (HR 0.74, 95% CI 0.55

–

0.99;

Fig. 2 )

; and

neutrophil-to-lymphocyte ratio 3 (HR 0.72, 95% CI 0.54

–

0.95). The CIs were wide for the subgroups because of the

small sample size. In addition, none of the interaction terms

(treatment baseline factors) were statistically significant.

3.3.

Site of relapse

According to blinded independent review, 97 patients in the

sunitinib arm and 122 patients in the placebo arm

developed distant disease recurrence. The most common

( 5%) sites of distant recurrence were lung and lymph node

( Table 2

). There was no difference in sites of recurrence

between the treatment arms. In 219 recurrences observed

across both arms, 89, 47, 36, and 25 occurred in lung, lymph

node, retroperitoneum, and liver, respectively. Only ten and

seven recurrences were observed in bone and brain,

respectively.

3.4.

Overall survival

At the cutoff date for the updated OS analysis (January 31,

2017), 67 patients in the sunitinib arm and 74 patients in the

placebo arm had died. The median follow-up time was 6.6 yr

in the sunitinib armand 6.7 yr in the placebo arm. The median

OS was not reached in either arm. The HR for sunitinib versus

placebo was 0.92 (95% CI 0.66

–

1.28;

= 0.6;

Fig. 3 )

Discussion

Results from this report on the S-TRAC study show that 71%

of patients completed 8 mo of adjuvant sunitinib treatment

and 56% completed the full year of treatment. Of the

treatment discontinuations reported for the sunitinib arm,

28% were related to AEs, which is similar to the

discontinuation rate reported for sunitinib in the metastatic

RCC setting

[6]

. Furthermore, the 28% discontinuation rate

reported in S-TRAC was over a median treatment duration of

12 mo, whereas in the metastatic setting, discontinuation

rates of 24% and 20% due to AEs were reported for pazopanib

and sunitinib, respectively, over a median treatment

duration of 8 mo

[4,6]

. For most patients, toxicities related

to adjuvant sunitinib were managed via supportive care and

a dose reduction or interruption. Nevertheless, there is still

a need to improve the management of some side effects in

the adjuvant setting. For example, hand-foot syndrome

occurred more frequently in the adjuvant than in the

metastatic setting

[6 – 8]

. Whether this is because of a more

physically active population receiving treatment in the

adjuvant setting or a more specific toxicity is not yet clear. In

addition, an alternative schedule (2 wk on treatment

followed by 1 wk off treatment) should be explored with

the aim of decreasing the frequency of side effects and

severity, as reported in the metastatic setting

[9] .

In addition to the positive outcome in the overall

population of the S-TRAC study, the majority of subgroups

defined according to baseline characteristics experienced

longer DFS on sunitinib compared to placebo, including the

prespecified subgroup of patients with higher risk of

recurrence (defined as T3, no or undetermined nodal

involvement, Fuhrman grade 2, and ECOG PS 1; or T4

and/or nodal involvement) compared to the overall

population, as well as the subgroup of patients with

Fuhrman grade 3/4.

This analysis has limitations in that all the subgroup

analyses were exploratory, and no adjustments for multi-

plicity were made. However, the results are consistent with

the primary analysis, showing a benefit for adjuvant

sunitinib treatment in patients at high risk of recurrent

RCC after nephrectomy.

Overall, 31% and 40% of patients in the sunitinib and

placebo arms, respectively, developed distant disease

recurrence. The most common sites of relapse included

lung, lymph node, and retroperitoneum. Bone and brain

metastases (1% each) were less common after adjuvant

sunitinib compared to the higher percentages documented

in metastatic RCC (30% for bone and 8% for brain)

[8,10,11] .

Knowing the patterns of recurrence in these

Table 1

–

S-TRAC selected baseline characteristics and summary of

study outcome

Sunitinib

Placebo

Patients assigned for

treatment/treated (

)

309/306

306/304

Median age, yr (interquartile range)

57 (49

–

64)

58 (51

–

66)

Male/female (%)

72/28

75/25

ECOG PS,

(%)

228 (74)

220 (72)

79 (26)

84 (28)

1 (0.3)

UCLA integrated staging system,

(%)

T3 low

115 (37)

112 (37)

T3 high

165 (53)

166 (54)

T4 or any T/N+

29 (9.4)

28 (9.2)

Patients who completed full 1-yr

treatment,

(%)

170 (56)

211 (69)

Median treatment duration, mo

(interquartile range)

12.4 (6.0

–

12.5) 12.4 (9.2

–

12.5)

Median daily dose, mg

(interquartile range)

45.9 (38.4

–

50)

50 (49

–

50.2)

Median DFS, yr (95% CI)

6.8 (5.8

–

NR)

5.6 (3.8

–

6.6)

DFS hazard ratio (95% CI)

for sunitinib vs placebo

0.76 (0.59

–

0.98)

CI = con

dence interval; DFS = disease-free survival; ECOG PS = Eastern

Cooperative Oncology Group performance status; NR = not reached;

UCLA = University of California Los Angeles.

T3, no or undetermined nodal involvement, no metastasis, any Fuhrman

grade, ECOG PS 0 or Fuhrman grade 1, ECOG PS 1.

T3, no or undetermined nodal involvement, no metastasis, Fuhrman

grade 2, ECOG PS 1.

T4 or any T with nodal involvement, no metastasis, any Fuhrman grade,

any ECOG PS.

According to blinded independent central review.

E U R O P E A N U R O L O GY 7 3 ( 2 0 18 ) 6 2

–

6 8