PhRMA Web Synopsis
Protocol A6181072 – 12 November 2009 - Final

PFIZER INC.
These results are supplied for informational purposes only.
Prescribing decisions should be made based on the approved package insert.
For publications based on this study, see associated bibliography.
PROPRIETARY DRUG NAME®/GENERIC DRUG NAME: Sutent® / Sunitinib malate
THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See USPINATIONAL CLINICAL TRIAL NO.: NCT00254540
PROTOCOL NO.: A6181072
PROTOCOL TITLE: Phase II Study of Single-Agent SU-011248 in the Treatment ofPatients with Renal Cell Carcinoma
Study Center(s): Twelve (12) centers in Japan

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Study Initiation and Completion Dates: 27 December 2005 to 25 February 2009
Phase of Development: Phase 2
Study Objectives:
Primary:
To determine the objective tumor response of single-agent SU-011248 at a dose of 50-mg
orally once daily for 4 consecutive weeks and 2 weeks off-treatment, repeated every 6 weeks
in renal cell carcinoma (RCC) for the pretreated population (subjects who had previously
been treated with one cytokine-based systemic therapy regimen for RCC) and the first-line
treatment population (subjects who had not had any prior systemic treatment for RCC).
Secondary: To evaluate the safety and tolerability of SU-011248
 To investigate trough plasma concentrations of SU-011248 and its primary active
metabolite, SU-012662
 To investigate plasma concentrations of pharmacodynamic markers (soluble proteins of
Vascular Endothelial Growth Factor [VEGF] and Soluble VEGFR2 [sVEGFR2]) that may
be associated with angiogenesis or tumor pathology
 To assess quality of life (QOL) To assess overall survival

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Protocol A6181072 – 12 November 2009 - Final

METHODS
Study Design: This was an open-label, single-arm, non-randomized, multicenter Phase 2
study evaluating the efficacy and safety of single-agent SU-011248 in subjects withmetastatic RCC.

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Subjects received SU-011248 in an open-label manner at a starting dose of 50-mg once dailyfor 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycleof 6 weeks. Subjects continued to receive SU-011248 until they met any of the study
discontinuation criteria.
Screening was performed within 21 days prior to the start of the study treatment. During thestudy treatment period, observations/tests were performed on Days 1, 14 (up to Cycle 4) and
28 of each cycle. Observation items were subject characteristics, concomitant
medications/therapies, treatment compliance, observation of tumor lesions mainly bycomputed tomography (CT) or magnetic resonance imaging (MRI) scan, answers to
EuroQOL EQ-5D (EQ-5D) questionnaire, pharmacokinetic and pharmacodynamic markers,
adverse events, hematology, biochemistry, body weight, body temperature, blood pressure,pulse rate, Eastern Cooperative Oncology Group (ECOG) performance status (PS), 12-leadelectrocardiogram (ECG) and echocardiogram or multigated acquisition (MUGA) scan. A
survival survey was conducted once a year for all subjects who received at least one dose of
study drug. The survey period lasted from the date of registration of the first subject until 3
years after the completion of subject registration.
Number of Subjects (Planned and Analyzed):
Planned: Fifty-one (51) subjects (26 for the pretreated population and 25 for the first-line
treatment population)
Analyzed: A total of 51 subjects composed of 26 for the pretreated population and 25 for the
first-line treatment population
Diagnosis and Main Criteria for Inclusion: Subjects aged 20 years or older who had
histologically proven RCC with metastases with a component of clear cell histology,
evidence of unidimensionally measurable disease as per Response Evaluation Criteria in
Solid Tumors (RECIST), and past history of nephrectomy. Both subjects who had notreceived any prior systemic treatment for RCC (first-line treatment population) and those
who had been previously treated with only one cytokine-based regimen for RCC (pretreatedpopulation) were enrolled in the study.
Study Treatment: Subjects received open-label SU-011248 orally for 4 consecutive weeks
followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. SU-011248
was taken orally in the morning without regard to meals beginning on Day 1 of the study.
Subjects were monitored for toxicity, and the SU-011248 dose could be adjusted according toindividual subject tolerance. Forms and strengths of the study drug were as follows:

SU-011248 12.5-mg capsule

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Protocol A6181072 – 12 November 2009 - Final

SU-011248 25-mg capsuleSU-011248 50-mg capsule

Efficacy Evaluations: The primary efficacy endpoint was objective response rate (ORR).
The ORR was defined as the proportion of subjects with confirmed complete response (CR)or partial response (PR) as the best overall response according to RECIST. To confirm CR
or PR, the subject had to meet the criteria for CR or PR at tumor reassessment not less than 4
weeks after the first documentation of response. The secondary endpoints were progressionfree survival (PFS), time to tumor progression (TTP), duration of response (DR), time totumor response (TTR), and overall survival (OS).
Patient-Reported Outcome Evaluations: Health-related quality of life (HRQOL) was
assessed using the EQ-5D questionnaire.

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Pharmacokinetic and Pharmacodynamic Evaluations: Trough plasma concentrations of
SU-011248, its active metabolite, SU-012662, and total drug (SU-011248 and SU-012662)
were assessed as pharmacokinetic markers. Plasma concentrations of soluble proteins(VEGF and sVEGFR2) were assessed as pharmacodynamic markers. Plasma samples forpharmacokinetic and pharmacodynamic analyses were collected prior to study treatment on
Days 1, 14 and 28 of Cycle 1, Days 1 and 28 of Cycle 2 and Day 28 of Cycle 3.
Safety Evaluations: The measurement and monitoring of adverse events, laboratory test
values, subjective symptoms/objective findings, body weight, body temperature, bloodpressure, pulse rate, ECOG PS, ECG and echocardiogram or MUGA scan were used toevaluate subject safety.
Statistical Methods: Two analysis sets were defined as follows:

The Intent-to-Treat (ITT) population was defined as all subjects treated with the study
drug at least once. The ITT population was the primary analysis set for efficacy and theanalysis set for safety.



The Per Protocol Set (PPS) was the population which excluded subjects who met at least
1 of the following criteria from the ITT population: subjects who deviate serious
inclusion/exclusion criteria or prohibited concomitant medication, subjects who received
less than 75% of the planned dose date through all cycles, and finally subjects whom theobjective tumor response was not evaluated after study drug dosing. The PPS was thesecondary analysis set for efficacy.

In the primary analysis of the primary efficacy endpoint, ORR and its 95% confidence
interval (CI) were calculated for each population (pretreated population, first-line treatment
population) based on the response according to Extramural Review Committee’s
assessments. The lower confidence limit was compared with the threshold value considered
to be clinically ineffective for each population (10% for the first-line treatment populationand 5% for the pretreated population). In the secondary analysis, the same analysis as theprimary analysis was performed for investigators’ assessments. Furthermore, a subgroup
analysis and a logistic regression analysis were performed on the ORR assessed by the
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Extramural Review Committee to examine the effects of covariates. In the analysis of thesecondary endpoints, descriptive statistics of PFS, TTP, and OS assessed by investigators
were calculated using Kaplan-Meier method. A subgroup analysis and a Cox proportional
hazards model analysis were also performed to examine the effects of covariates.
In the pharmacokinetic analysis, descriptive statistics were calculated for trough plasma
concentrations of SU-011248, SU-012662, and total drug. In the pharmacodynamic analysis,
descriptive statistics were calculated for plasma concentrations of pharmacodynamic markers(VEGF and sVEGFR2), and the relationship between the pharmacodynamic markers andantitumor activity was explored by calculating descriptive statistics for the percent change
from baseline to each sampling time point for each subgroup based on the best overall
response. The percent change from baseline on Day 28 of Cycle 3 was compared among thesubgroups based on the best overall response by the Wilcoxon’s rank sum test (=0.05).
In the safety analysis, adverse events, laboratory abnormalities, and other safety parameters
were analyzed. The severity of adverse events was classified according to the National
Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
RESULTS
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Subject Disposition and Demography: Subject disposition is shown in Table S1.
Table S1. Subject Disposition and Subjects Analyzed [Number of Subjects (%)]
Population
Enrolled
TreatedCompleted
Discontinued
Analyzed for Efficacy
Intent-to-Treat (ITT) population
Per Protocol Set (PPS)
Analyzed for Pharmacokinetics
Analyzed for Pharmacodynamics
Analyzed for Safety (ITT)
Adverse events
Laboratory data

First-line Treatment
25
25
6
19

Pretreated
26
26
4
22

Overall
51
51
10 (19.6)
41 (80.4)

25
15 (60.0)
25
25
25
25
25

26
17 (65.4)
26
26
26
26
26

51 (100)
32 (62.7)
51 (100)
51 (100)
51 (100)
51 (100)
51 (100)

Of 51 subjects enrolled, 11 subjects (44.0%) in the first-line treatment population and 21
subjects (80.8%) in the pretreated population were males. Mean age was 56.6 years (range:
33 to 76 years) in the first-line treatment population, and 61.1 years (range: 34 to 77 years) inthe pretreated population; 7 subjects (28.0%) in the first-line treatment population and 11
subjects (42.3%) in the pretreated population were 65 years or older. Twenty subjects(80.0%) in the first-line treatment population and 22 subjects (84.6%) in the pretreatedpopulation had an ECOG PS of 0, and 5 subjects (20.0%) in the first-line treatment
population and 4 subjects (15.4%) in the pretreated population had an ECOG PS of 1. In thefirst-line treatment population and the pretreated population, the median number of cycles
was 6.0 cycles and 9.5 cycles, respectively. The median treatment periods (off-treatment

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Protocol A6181072 – 12 November 2009 - Final

period excluded) were 163.0 days in the first-line treatment population and 192.0 days in the
pretreated population.
Efficacy Results: The ORR (95% CI) after the completion of Cycle 4 in the ITT population
based on the Extramural Review Committee’s assessment, the primary analysis of the
primary efficacy endpoint, was 48.0% (95% CI: 27.8 to 68.7%) in the first-line treatment
population and 46.2% (95% CI: 26.6 to 66.6%) in the pretreated population. The lower
confidence limit for the ORR exceeded the threshold value for each population (10% for the
first-line treatment population and 5% for the pretreated population). The ORR (95% CI)
after the completion of Cycle 4 in the ITT population based on the investigators’
assessments, as the secondary analysis, was 48.0% (95% CI: 27.8 to 68.7%) in the first-line
treatment population and 46.2% (95% CI: 26.6 to 66.6%) in the pretreated population. The
ORR (95% CI) after the completion of study in the ITT population based on theinvestigators’ assessment was 52.0% (95% CI: 31.3 to 72.2%) in the first-line treatment
population and 53.8% (95% CI: 33.4 to 73.4%) in the pretreated population (Table S2).
Table S2. Summary of Objective Response Rate [ITT Population]

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Population
After the completion of Cycle 4
Extramural Review Committee’s
assessment-based responder a
Objective Response Rate (%) [95% CI]
Investigators’ assessment-based responder a
Objective Response Rate (%) [95% CI]
After the completion of study
Investigators’ assessment-based responder a
Objective Response Rate (%) [95% CI]a) CR or PR
CI = Confidence intervalFirst-line Treatment(N=25)

Pretreated(N=26)Overall(N=51)

12
48.0 [27.8, 68.7]
1248.0 [27.8, 68.7]

1246.2 [26.6, 66.6]
12
46.2 [26.6, 66.6]

24
47.1 [32.9, 61.5]
24
47.1 [32.9, 61.5]

13
52.0 [31.3, 72.2]

14
53.8 [33.4, 73.4]

27
52.9 [38.5, 67.1]

During treatment with SU-011248 (including 28 days after the completion of treatment) andprior to the start of antitumor therapy other than SU-011248, progressive disease (PD) was
experienced by 14 subjects (56.0%) in the first-line treatment population and 18 subjects(69.2%) in the pretreated population. Median PFS was 53.0 weeks and 46.0 weeks for the
first-line treatment and the pretreated populations, respectively. Only 1 subject died while on
study, but evidence of PD was documented beforehand, and thus TTP and PFS wereidentical.
According to investigators’ assessments, median TTR was 10.0 weeks for the first-line
treatment population and 10.5 weeks for the pretreated population. Median DR was 111.6
weeks and 38.1 weeks for the first-line treatment and the pretreated populations, respectively.
All-causality death was reported in 14 subjects (56.0%) for the first-line treatment population,and 14 subjects (53.8%) for the pretreated population. Median OS was 143.4 weeks and
141.0 weeks for the first-line treatment and the pretreated populations, respectively.
Patient-Reported Outcome Results: Subjects’ HRQOL was evaluated using the EQ-5D
questionnaire. For the EQ-5D index score, the range of mean change at each endpoint frombaseline was from -0.1573 to 0.0375 in the first-line treatment population and from -0.0974

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Protocol A6181072 – 12 November 2009 - Final

to 0.0513 in the pretreated population. For the EQ-5D-VAS score, the range of mean change
at each endpoint from baseline was from -12.35 to 2.71 in the first-line treatment populationand from -11.82 to 4.17 in the pretreated population. Assessment of HRQOL by the EQ-5D
questionnaire showed that the EQ-5D index score and EQ-5D-VAS in each cycle trended
lower on treatment with SU-011248 and recovered during the off-treatment periods in bothsubject populations.
Pharmacokinetic and Pharmacodynamic Results: The median plasma troughconcentrations of total drug reached therapeutically effective levels estimated from thenonclinical study results (>50 ng/mL) on Day 14 of Cycle 1 in both subject populations, andsuch levels were sustained during the subsequent treatment period. The plasma troughconcentrations of SU-011248 and SU-012662 on Days 14 and 28 of Cycle 1 werecomparable to those on Day 28 of Cycles 2-3, which suggested that repeated treatment does
not result in further accumulation of the drug in plasma.

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Plasma VEGF levels increased and sVEGFR2 levels decreased during treatment with
SU-011248, and both VEGF and sVEGFR2 levels nearly returned to baseline during a
2-week off-treatment period. A comparison of the rate of change from baseline to Day 28 ofCycle 3 based on the best overall response by the Wilcoxon’s rank sum test (5% significancelevel) did not reveal statistically significant differences in both subject populations.
Safety Results: An overall summary of adverse events is shown in Table S3.
Table S3. Overall Summary of Adverse Events
Population
Causality

First-line Treatment(N=25)
AllTreatmentcausality
related817
746

Pretreated(N=26)
AllTreatmentcausality
related956
854

Overall(N=51)
AllTreatmentcausality
related
1773
1600

Number of AE
Number of subjects (%)
AE
25 (100)
25 (100)
26 (100)
26 (100)
51 (100)
25 (100)
25 (100)
26 (100)
26 (100)
51 (100)
AE of Grade 3 or 4a12
(48.0)
11(44.0)
16(61.5)
15(57.7)
28(54.9)
Serious AE
AE of Grade 500
1 (3.8)0
1 (2.0)Discontinuation due to AE
6 (24.0)
6 (24.0)
9 (34.6)
7 (26.9)15 (29.4)
Dose Schedule Modification
22 (88.0)
22 (88.0)
24 (92.3)
24 (92.3)
46 (90.2)
due to AE
AE: Adverse eventa) One subject who developed a SAE after informed consent was obtained, but prior to study drug
administration was excluded.

51 (100)
51 (100)
26 (51.0)013 (25.5)
46 (90.2)

Fifty-one (100%) of 51 subjects had a total of 1773 all-causality adverse events, and 51(100%) of 51 subjects had a total of 1600 treatment-related adverse events. The mostcommon all-causality adverse events (>20% of subjects in all-causality, any-grade) aresummarized in Table S4.

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Protocol A6181072 – 12 November 2009 - Final

Table S4. Treatment-Emergent Adverse Events Reported in >20% of Subjects[Number of Subjects (%)]
Total
(N=51)
47 (92.2)
44 (86.3)
41 (80.4)
37 (72.5)
37 (72.5)
36 (70.6)
36 (70.6)
36 (70.6)
35 (68.6)
34 (66.7)
31 (60.8)
31 (60.8)30 (58.8)
29 (56.9)
29 (56.9)
28 (54.9)
27 (52.9)
27 (52.9)
26 (51.0)
26 (51.0)
26 (51.0)
25 (49.0)
24 (47.1)
24 (47.1)
23 (45.1)
21 (41.2)
20 (39.2)
19 (37.3)
18 (35.3)
17 (33.3)
16 (31.4)
16 (31.4)
15 (29.4)
14 (27.5)
13 (25.5)
13 (25.5)
12 (23.5)
12 (23.5)
12 (23.5)
12 (23.5)
11 (21.6)
11 (21.6)
11 (21.6)

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MedDRA Preferred Term (version 11.1)
Platelet count decreased
White blood cell count decreased
Neutrophil count decreased
Anorexia
Skin discolouration
Blood lactate dehydrogenase increased
Lipase increased
Lymphocyte count decreased
Aspartate aminotransferase increased
Fatigue
Hypertension
Pyrexia
Diarrhoea
Blood creatinine increased
Rash
Dysgeusia
Alanine aminotransferase increased
Palmar-plantar erythrodysaesthesia syndrome
NauseaStomatitis
Blood amylase increased
Haemoglobin decreased
Face oedema
Nasopharyngitis
Hypothyroidism
Oedema peripheral
MalaiseBlood alkaline phosphatase increased
Blood albumin decreased
Epistaxis
Vomiting
Blood bilirubin increased
Anaemia
Blood phosphorus decreased
Eyelid oedema
Headache
Cheilitis
Dyspepsia
Blood calcium decreased
Back pain
Constipation
CoughProtein total decreased

Twenty eight subjects (54.9%) experienced serious adverse events. All serious adverse
events reported in this study are summarized in Table S5. One subject died during this study,
and the cause of death was tumor progression and renal cell carcinoma (RCC), which wasconsidered to be unrelated to study treatment.

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Protocol A6181072 – 12 November 2009 - Final

Table S5. Serious Adverse Events[Number of Subjects (%)]
Total
(N=51)
5 (9.8)5 (9.8)4 (7.8)4 (7.8)3 (5.9)3 (5.9)3 (5.9)2 (3.9)2 (3.9)2 (3.9)2 (3.9)2 (3.9)2 (3.9)2 (3.9)2 (3.9)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)1 (2.0)090177e180fde6e6\Approved\Approved On: 21-Dec-2009 04:48

MedDRA Preferred Term (version 11.1)
Platelet count decreased
Dehydration
NauseaAnorexia
Vomiting
Fatigue
Aspartate aminotransferase increased
Anaemia
Atrial fibrillation
Hypothyroidism
MalaiseAlanine aminotransferase increased
Blood alkaline phosphatase increased
Neutrophil count decreased
White blood cell count decreased
Myocardial infarction
Sick sinus syndrome
Thyroiditis
Anal fistulaAnal ulcer
Ascites
Diarrhoea
Gastrointestinal obstruction
Melaena
Upper gastrointestinal haemorrhage
Pyrexia
Bile duct stone
Cholecystitis
Hepatic function abnormal
Hyperbilirubinaemia
SepsisBlood bilirubin increased
Ejection fraction decreased
Hyperamylasaemia
Hypercalcaemia
Hypomagnesaemia
Hyponatraemia
Neoplasm progression
Headache
Proteinuria
Renal failure acute
Renal impairment
Cough
Dyspnoea
Haemothorax
HypoxiaInterstitial lung disease
Pleural effusion
Pulmonary oedema
Drug eruption
Hypertension

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Protocol A6181072 – 12 November 2009 - Final

Fifty-one (100%) subjects experienced Grade 3 adverse events. The most common Grade3 adverse events (20%) included platelet count decreased, neutrophil count decreased,
lipase increased, lymphocyte count decreased, and fatigue. The majority of these adverse
events were considered treatment-related.
When summarized by treatment cycles, the overall incidences of Grade 3 adverse eventswere 65.8% to 84.3% (Cycle 1: 84.3%, Cycle 2: 74.4%, Cycle 3: 65.8%, Cycle 4: 77.1%),
that did not show clear increase in frequency over time. The incidence of Grade 3 adverse
events by MedDRA preferred term revealed a gradual increased incidence of diarrhoea(Cycle 1: 0%, Cycle 2: 2.3%, Cycle 3: 2.6%, Cycle 4: 5.7%) and palmar-plantar
erythrodysaesthesia syndrome (Cycle 1: 0%, Cycle 2: 7.0%, Cycle 3: 7.9%, Cycle 4: 11.4%)
over time.

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Forty-six subjects (90.2%) required dose schedule modification (i.e., dosing interruption
and/or dose reduction) due to an adverse event. The most common adverse events which led
to dose schedule modification included platelet count decreased (26 subjects, 51.0%),
neutrophil count decreased (23 subjects, 45.1%), white blood cell count decreased (15subjects, 29.4%), fatigue (13 subjects, 25.5%), and palmar-plantar erythrodysaesthesia
syndrome (11 subjects, 21.6%). Most of the adverse events led to dose schedule
modification were well-managed with or without standard medical therapy.
Discontinuation due to an adverse event was reported in 15 subjects (29.4%). Adverse
events leading to discontinuation of the study treatment are listed in Table S6.
Table S6. Adverse Events Leading to Discontinuation of the Study Treatment
Sex

Age
Dose
(years) (mg/day)Male 65
25
Female 60
25
Female 69
25
Female 76
37.5
Male 70
50
Female 35

50

Female 34
Male 73
Male 62
Male 58

37.5
50
25
50

Male 73
Male 58
Female 69
Male 77
Male 76

25
25
25
37.5
50

MedDRA Preferred Term(version 11.1)
Ejection fraction decreased
Stomach discomfort
MalaiseEjection fraction decreased
Atrial fibrillation
Thyroiditis
Forced expiratory volume decreased
Dyspnoea
Hypoxia
Pleural effusion
Respiratory gas exchange disorder
Neoplasm progression
Hypertension
Blood calcium increased
ChillsFatiguePyrexia
Hypothyroidism
Anaemia
Fatigue
Interstitial lung disease
Anorexia
Hypertension

Page 9Causality

OutcomeRelatedRelatedRelatedRelatedRelatedRelatedRelatedRelatedRelatedRelatedRelatedNot related
RelatedRelatedRelatedRelatedRelatedRelatedNot related
RelatedRelatedRelatedRelatedNot recovered
Not recovered
Not recovered
Not recovered
Not recovered
Not recovered
Not recovered
Recovered
Recovered
Recovered
Not recovered
Death
Recovered
Not recovered
Recovered
Recovered
Recovered
Not recovered
Not recovered
Not recovered
Recovered
Not recovered
Not recoveredPhRMA Web Synopsis
Protocol A6181072 – 12 November 2009 - Final

Hypertension and pyrexia were reported in more than half of the subjects, and those events
led to the study discontinuation of 3 subjects (hypertension in 2 subjects; pyrexia in 1
subject); no significant adverse change was found in pulse rate and body weight. ECG QT
corrected interval prolonged was experienced by 2 subjects (3.9%); however, both of theevents were neither serious nor clinically significant and resolved without dose modification
or discontinuation. The number of subjects who experienced left ventricular ejection fraction
decreased did not increase over time. Two subjects experienced ejection fraction decreased
as adverse events which led to discontinuation, 1 of which was serious, but abated after
discontinuation of treatment.
CONCLUSIONS: SU-011248 had antitumor activity with an ORR of 48.0% in those subjects withmetastatic RCC who had not had any prior systemic treatment, and with an ORR of 46.2%
in those subjects who had previously been treated with one cytokine-based systemic
therapy regimen.

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 The AE profile of SU-011248 at 50-mg daily on a 4-weeks on/2-weeks off schedule was
generally tolerable and manageable in both advanced-stage RCC subject populations.
 The median plasma trough concentrations of total drug reached therapeutically effective
levels estimated from the nonclinical study results (>50 ng/mL) on Day 14 of Cycle 1 inboth subject populations, and these levels were sustained during the subsequent treatment
period without further accumulation of SU-011248 and SU-012662.
 There was no clear relationship between changes in pharmacodynamic markers, such asplasma VEGF and sVEGFR2 levels, and the best overall response.
 Subjects’ HRQOL trended lower on treatment with SU-011248 and recovered during theoff-treatment period.
 Median overall survival was 143.4 weeks in the first-line treatment population and 141.0
weeks in the pretreated population.

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