EURURO Vol. 72 No. 3

after first progression. Best overall response was determined based on

response up to first progression. The 95% confidence interval (CI) on the

objective response rate (ORR) was determined using the Clopper-

Pearson method. Descriptive statistics after first progression included

assessment of antitumor activity overall and by best overall response

before first progression. OS was estimated overall and from 4 wk post

initial progression to death using the Kaplan-Meier method; median and

corresponding two-sided 95% CI were reported using Brookmeyer and

Crowley methodology. Analyses were performed using SAS v.9.2 (Cary,

NC, USA).

Results

Among 406 nivolumab-treated patients, 316 (78%) had

progressed and 90 (22%) had not progressed. Of 316 patients

with progression, 171 were recommended for and con-

sented to treatment beyond progression and 153 (48%)

were ultimately TBP; 163 (52%) were NTBP (including

18 patients who were treated briefly (

[2_TD$DIFF]

4 wk) beyond

progression (Supplementary Fig. 1).

Baseline characteristics were generally similar, except

more patients had better Karnofsky performance status

(KPS) in those TBP versus NTBP

( Table 1

). Median (95% CI)

duration of nivolumab treatment from randomization to

discontinuation or death was 8.8 mo (7.4–10.2, TBP) and

2.8 mo (1.9–3.3, NTBP).

Of patients NTBP, 76% went on to receive subsequent

therapy. Subsequent systemic therapy was received by 68%

of all patients NTBP, of which the most common was

everolimus (34%).

3.1.

Disease characteristics and QoL from randomization to

first progression

Median (95% CI) duration of nivolumab treatment from

randomization to first progression was 2.7 mo (1.9–3.8) for

patients TBP and 2.4 mo (1.9–3.3) for patients NTBP. From

randomization to first progression, ORR (95% CI) was 20%

(14–28) for those TBP and 14% (9–20) for those NTBP; best

overall response was generally similar

( Table 2

). Median

time to response was 1.9 mo and 3.7 mo and duration of

response was 5.6 mo and 7.0 mo for patients TBP and NTBP,

respectively

( Table 2

Table 2 – Characteristics at first progression

Nivolumab

Characteristics

Patients treated

beyond

progression

(

= 153)

Patients not

treated beyond

progression

(

= 163)

KPS,

) a

111 (73)

81 (50)

70 or 80

41 (27)

78 (48)

1 (1)

4 (2)

Changes in KPS,

(%)

Deterioration

26 (17)

44 (27)

Improvement

24 (16)

12 (7)

Target lesion status at first progression,

(%)

Increase in target lesion

s b

84 (55)

71 (44)

Appearance of new lesions

63 (41)

72 (44)

Increase in target lesions

and appearance of new lesions

18 (12)

25 (15)

Site of new lesions,

(%)

Lung

21 (14)

22 (13)

Lymph node

15 (10)

15 (9)

Bone

8 (5)

24 (15)

Liver

8 (5)

11 (7)

Objective response rate,

% (95% CI)

20 (14–28)

14 (9–20)

Best overall response,

(%)

Complete response

(0)

1 (1)

Partial response

31 (20)

22 (14)

Stable disease

51 (33)

65 (40)

Progressive disease

70 (46)

64 (39)

Unable to determine

1 (1)

11 (7)

Median time to response,

mo (range)

1.9 (1.7–9.2)

3.7 (1.4–11.1)

Median duration of

response, mo (95% CI)

5.6 (3.9–7.5)

7.0 (2.2–7.7)

Quality of life (FKSI-DRS),

median (first quartile,

third quartile

) c

32.0 (28.0, 34.0) 27.0 (24.0, 32.0)

CI = confidence interval; FKSI-DRS = Functional Assessment of Cancer

Therapy-Kidney Symptom Index-Disease Related Symptoms;

KPS = Karnofsky performance status.

Defined as the performance status at or before and closest to the time of

progression.

At least 20% increase in the sum of diameters of target lesions, taking as

reference the smallest sum on study.

= 129 treated beyond progression and

= 58 not treated beyond

progression.

Table 1 – Demographic and baseline characteristics at study entry

Nivolumab

Characteristics

Patients

treated beyond

progression

(

= 153)

Patients not

treated beyond

progression

(

= 163)

Median age, yr (range)

62 (29–85)

63 (23–85)

Sex,

(%)

Men

116 (76)

128 (79)

MSKCC risk group,

(%)

Favorable

58 (38)

50 (31)

Intermediate

70 (46)

82 (50)

Poor

25 (16)

31 (19)

KPS,

(%)

110 (72)

102 (63)

70 or 8

0 a

43 (28)

60 (37)

No. of evaluable sites

, b n

(%)

21 (14)

23 (14)

132 (86)

140 (86)

Prior radiotherapy,

(%)

39 (25)

49 (30)

No. of prior systemic antiangiogenic regimens,

(%)

113 (74)

131 (80)

2 c

38 (25)

32 (20)

Quality of life (FKSI-DRS),

median (first quartile,

third quartile

) d

32.0 (27.0, 34.0)

30.5 (26.5, 33.0)

FKSI-DRS = Functional Assessment of Cancer Therapy-Kidney Symptom

Index-Disease Related Symptoms; KPS = Karnofsky performance status;

MSKCC = Memorial Sloan Kettering Cancer Center.

All patients had a KPS of 70 at time of study entry but KPS decreased to

70 in one patient at randomization who was subsequently not treated

beyond progression.

Included target and nontarget lesions.

Two patients who were treated beyond progression had

2 prior regimens.

= 129 treated beyond progression and

= 58 not treated beyond

progression.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 3 6 8 – 3 7 6

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