samo forome post-esmo · cediranib plus platinum-based ct followed by maintainance cediranib...

SAMO FoROMePost-ESMO

Gynecological Cancers

C. SessaIOSI, Bellinzona

Lucerne, October 17th, 2013

Update on antivascular agents

First line ICON 7

SAMO FoROMePost-ESMO 2013

Relapse ICON 6

TrebananibAurelia

Ovarian Carcinoma:Classical Evolution of the disease

(Late) Diagnosis(Late) Diagnosis

IntervalIntervalDebulkingDebulking

DeathDeathCR or PRCR or PR ProgressionProgression

> 6> 6 mnthsmnths

ProgressionProgression< 6< 6 mnthsmnths

Pazopanib: AGO OVAR16 Bev: AURELIA

SymptomsSymptoms ChemotherapyChemotherapy

Primary DebulkingPrimary Debulking

PlatinPlatin--sensitivesensitive

PlatinPlatin--resistantresistant

Supportive CareSupportive Care

MaintenanceMaintenance

MaintenanceMaintenanceBevacizumab: GOG218, ICON7Nintedanib: AGO OVAR12

VEGF

Bev: OCEANSCediranib: ICON6

ANG

Trebananib: ENGOT-ov2

PARP

Olaparib: PARP19

Trebananib: Trinova-1

ICON7: Final overall survival results in the GCIGphase III randomized trial of bevacizumab inwomen with newly diagnosed ovarian cancer

4

AM Oza, TJ Perren, AM Swart, W Schröder, E Pujade-Lauraine, H Havsteen,P Beale, A Cervantes, AC Embleton, M Parmar

on behalf of the ICON7 investigators(MRC/NCRI, AGO-OVAR, GINECO, NSGO, ANZGOG, GEICO, NCIC-CTG)

Schema

Paclitaxel 175 mg/m2

Carboplatin AUC 5 or 6


R

1:1

• FIGO stage I–IIA(clear cell or grade 3)or FIGO stage IIB–IV

• Surgically debulkedhistologicallyconfirmed OC

5

Stratification variables:• Stage & extent of debulking (I–III debulked ≤1cm vs I–III debulked >1 cm vs IV and

inoperable stage III)• Timing of intended treatment start (≤4 vs >4 weeks after surgery)• GCIG group


Paclitaxel 175 mg/m2

18 cycles (12 months)Bevacizumab 7.5 mg/kg q3w

OC = epithelial ovarian, primary peritoneal or fallopian tube cancer

n=1528

Dec 2006 to Feb 2009

ICON7 was powered for both PFS and OS, designed to detect:

• PFS HR = 0.78 (684 events; 90% power)

• OS HR = 0.81 (715 events; 80% power)

Median follow-up, PFS OS events (% of

Overview ofanalyses

6

Median follow-up,months

PFSevents

OS events (% ofrequired events)

Mature PFS analysis

(cut-off Feb 28, 2010; ESMO 2010)

19 759 241 (34%)

Updated interim OS analysisrequested by regulatory authorities

(cut-off Nov 30, 2010; ASCO 2011)

28 934 378 (53%)

Final OS analysis 49 1080 714 (100%)

Primary analysis(2010)

7

100

75

50

25

Aliv

ew

ith

ou

tp

rogre

ssio

n(%

)

Primary PFS(all patients)

HR = 0.81(95% CI 0.70–0.94)

p=0.0041

Aliv

e(%

)

First interim OS(all patients)

HR = 0.81(95% CI 0.63–1.04)

p=0.098

100

75

50

25

0

Aliv

ew

ith

ou

tp

rogre

ssio

n(%

)

Time (months)0 3 6 9 12 15 18 21 24 27 30

17.3 19.0p=0.0041

Time (months)0 3 6 9 12 15 18 21 24 27 30

p=0.0980

Time (months)

10.5 15.9

100

75

50

25

0

Aliv

ew

ith

ou

tp

rogre

ssio

n(%

)

PFS: High-risk

0 3 6 9 12 15 18 21 24 27 30

Perren TJ, et al. NEJM 2011

1.00

0.75

Pro

port

ion

aliv

ew

ithoutpro

gre

ssio

nPFS (2013 update)

Control Research ∆

Events, n (%) 526 (69) 554 (73)Restricted mean,months

27.7 29.2 +1.6

Median, months 17.5 19.9 +2.4

Log-rank test p=0.25

Non-proportionality test: p<0.0001

8

Number at riskControl 764 484 294 239 198 66Research 764 604 314 226 182 54

0.50

0.25

0

Pro

port

ion

aliv

ew

ithoutpro

gre

ssio

n

Time (months)0 6 12 18 24 30 36 42 48 54 60


HR (95% CI) 0.93 (0.83–1.05)

BEV exposure 19.917.5 CT scans as clinically indicated

1.00

0.75

Pro

port

ion

aliv

ew

ithoutpro

gre

ssio

n

PFS (2013 update):High-risk (n=502)


Events (%) 228 223

Restricted mean,months

15.9 20.0 +4.1

Non-proportionality test: p<0.0001

9

Stage III suboptimally debulked , any stage IV or no debulking surgery

Total

451 (90)


0.50

0.25

0

Pro

port

ion

aliv

ew

ithoutpro

gre

ssio

n

Time (months)0 6 12 18 24 30 36 42 48 54 60

Median, months 10.5 16.0 +5.5


HR (95% CI) 0.73 (0.61–0.88)

16.010.5

BEV exposure

Final OS: High-risk(n=502)

1.00

0.75

Pro

port

ion

aliv

e


Deaths (%) 174 158Restrictedmean, months

34.5 39.3 +4.8

Median, months 30.3 39.7 +9.4Log-rank test p=0.03HR (95% CI) 0.78 (0.63–0.97)

Non-proportionality test:p=0.0072

Stage III suboptimally debulked , any stage IV or no debulking surgery

10

Total

332 (66)


0.50

0.25

0

Pro

port

ion

aliv

e

Time (months)0 6 12 18 24 30 36 42 48 54 60

39.730.3

9.4

BEV exposure

Conclusions

Final OS analyses for ICON7 show:

• In the entire population:– OS curves are non-proportional restricted mean is the appropriate

statistic for the difference (0.9 months)

– No evidence of a difference in OS (log-rank p=0.85)

– Any OS difference is not clinically meaningful

11

– Any OS difference is not clinically meaningful

• In the high-risk subgroup (suboptimally debulked stage III,stage IV and non-operated patients):– Significant OS improvement with bevacizumab 7.5 mg/kg

(log-rank p=0.03, non-proportionality test p=0.007)

– 4.8 months’ improvement by restricted means

– 9.4 months’ median difference with HR 0.78 (95% CI 0.63–0.97)

– OS difference in high-risk subgroup is clinically meaningful

Randomised double-blind phase IIItrial of cediranib (AZD 2171) in

relapsed platinum sensitive ovariancancer: Results of the ICON6 trial.cancer: Results of the ICON6 trial.

An academic sponsored GCIG trial

Ledermann JA, Perren T, Raja FA, Embleton AC, Rustin GJS,Jayson G, Kaye SB, Swart AM, Vaughan M, Hirte H

on behalf of the ICON 6 Collaborators(NCRN, NCIC-CTG, ANZGOG, GEICO)

ICON6: Cediranib with platinum-basedchemotherapy in ‘platinum-sensitive’relapsed ovarian cancer

Study schema

Arm A(Chemo only)

Arm B(Concurrent)

Arm C(Maintenance)

Relapse > 6 monthsafter completion of first

line platinum-basedchemotherapy

Randomise2 : 3 : 3

6 Cycles platinum-basedChemotherapy Carboplatin/paclitaxel Carboplatin/gemcitabine Single agent platinum

Maintenance phase

Treatment continued to 18 months oruntil progression (>18 for patients

continuing to benefit)

Continueplacebo

Switch toplacebo

Maintenancecediranib

Chemotherapy +cediranib

Chemotherapy +placebo

(Chemo only) (Concurrent) (Maintenance)

Chemotherapy +cediranib

Chronology and Statistical Design – ICON 6

Dec 2007 Trial opened – Cediranib 30mg reduced to 20mg

Nov 2009 Completed stage I (toxicity phase)

Expanded stage II (efficacy phase)

Sept 2011 AZ ceased development of cediranib

PFS instead of OS as primary endpoint

Primary comparison: Arm A vs Arm CSecondary: OS and Arm A vs Arm B vs Arm C

Dec 2011 Trial closed 486 patients176 PFS events occurred around Q4 2012

Chemo onlyn=118

Concurrentn=174

Maintenancen=164

Randomisation ratio 2 3 3

Age

Median (range) 62 (37-77) 62 (30-85) 62 (32-86)

ECOG status

0 69 (59%) 109 (63%) 95 (58%)

1 47 (41%) 64 (37%) 68 (42%)

Baseline characteristics

1 47 (41%) 64 (37%) 68 (42%)

Time since last chemotherapy

6-12 months 43 (36%) 59 (34%) 50 (30%)

>12 months 75 (64%) 115 (66%) 114 (70%)

Previous paclitaxel

Yes 103 (87%) 154 (89%) 148 (90%)

VEGF/EGFR

Bevacizumab 6 (5%) 9 (5%) 9 (5%)

Erlotinib 0 - 1 (1%) 0 -

0.50

0.75

1.00

Chemotherapy

Maintenance

Restricted mean survival time increases by3.1 months with maintenance treatment

Chemo. Maint.

PFS events, n (%) 112 (94.9) 139 (84.8)

Median, months 8.7 11.1


HR (95% CI) 0.57 (0.45 – 0.74)

Test for non-proportionality p=0.024

Restricted means, months 9.4 12.5

Progression-free survival – arms A vs. C

0.00

0.25

164 148 65 21 7118 90 24 8 3

.

0 3 6 9 12 15 18 21 24Months

Chemo.Maint.

3.1 months with maintenance treatment

0.50

0.75

1.00Chemo. Conc. Maint.

PFS events, n (%) 112 (94.9) 152 (87.4) 139 (84.8)

Median, months 8.7 10.1 11.1

Log-rank test (trend) p=0.0003

HR vs. Chemo only(95% CI)

0.67(0.53–0.87)

0.57(0.44–0.74)

Restricted means, months 9.4 11.4 12.5

Progression-free survival – all three arms

Chemotherapy

Maintenance

0.00

0.25

164 148 65 21 7174 152 53 20 12118 90 24 8 3

.

0 3 6 9 12 15 18 21 24Months

Conc.

Maint.

Chemo.

Concurrent

0.50

0.75

1.00

Chemo. Maint.

OS events, n (%) 63 (53.3) 75 (45.7)

Restricted mean survival time increasesby 2.7 months with maintenancetreatment (over two years)

Overall survival

Chemotherapy

Maintenance

0.00

0.25

164 159 139 89 48 2222118 106 89 46 27 1111

.

0 6 12 18 24 30Months

OS events, n (%) 63 (53.3) 75 (45.7)

Median, months 20.3 26.3


HR (95% CI) 0.70 (0.51 – 0.99)

Test for non-proportionality p=0.0042

Restricted means, months 17.6 20.3

Chemo.Maint.

0

25

50

75

100

Chemo only Concurrent Maintenance

%

p=0.004

Hypertension

0

25

50

75

100


p=<0.001

Diarrhoea

Specific Adverse Events – during chemotherapy

Grade

4 p=0.004 p=<0.001

0

25

50

75

100


%

p=0.008

Nausea

0

25

50

75

100


p=0.59

Fatigue

1

2

3

4

Conclusions – ICON 6

1. Cediranib plus platinum-based CT followed by maintainancecediranib provides a statistically significant benefit compared toCT alone in recurrent platinum-sensitive ovarian cancer

PFS improved by 3.1 mos HR:0.57 (0.45-0.74)PFS improved by 3.1 mos HR:0.57 (0.45-0.74)

OS improved by 2.7 mos HR:0.70(0.51-0.99)

2. Strong evidence that cediranib has an effect on PFS bothduring and after CT

Phase III studies in ovarian cancerwith targeted drugs

Phase III studies in ovarian cancerwith targeted drugs

First line Platin-sensitive Pl-resist

GOG218Bev

ICON7Bev

AGOPazo

OCEANSBev

ICON6Ced

PARP***Ola

AURELIABev

PFS ** 3.8 1.7 5.6 4.0 3.1 4.0 3.3≠

PFS HR 0.72 0.81 0.77 0.84 0.57 0.35 0.48

OS 0.4 0.9 NA - 1.8 2.7 2.0 3.3

OS HR 0.91(NS)***

NS 0.99(NS)

1.03(NS)

0.70 0.88(NS)

0.85(NS)

≠

Burger NEJM 2011; Perren NEJM 2011 – Oza ECC 2013 for OS; du Bois ASCO 2013; Aghajanian JCO 2012;Ledermann ECC 2013; Ledermann ASCO 2013; Pujade-Laurraine ASCO 2012 - Witteveen ECC 2013

* : difference in months; **NS: Not Significant; Significant unless stated NS; *** Phase II

How to explain the OS difference withcediranib in ICON 6?


Carbo Carbo

-Gem

Carbo

-Gem

Carbo

-Gem

Carbo

Comb

Carbo

Comb-Gem -Gem -Gem

+ Bev

Comb Comb

+ Ced

Maint

PFS 5.8 8.6 8.4 12.4 8.7 11.1

OS 17.3 18 35.2 33.3 20.3 26.3

Pfisterer JCO 2006; Aghajanian JCO 2012 ; Ledermann, ICON6, ECC 2013 LBA 10

Questions:

1. What was the median number of lines givenafter progression in ICON 6?


after progression in ICON 6?

2. Does a shorter post-progression survival(PPS) make a significant OS difference more

likely?

What is Post Progression Survival (PPS)?

Post Progression Survival: Time from disease progression till death

Progression DeathOS

Start

www.esmo2012.org

PFS PPS

OS

A 15 month difference in overall survivalbetween the OCEAN trial and ICON 6 might


www.esmo2012.org

between the OCEAN trial and ICON 6 mightexplain why OS is significant in ICON 6 and not

in the OCEAN trial.

Cediranib in relapsed ovarian cancer – ICON 6

Key messages

• Cediranib is another VEGF targeting drug in platinum-sensitiveovarian cancer

• Cediranib is associated with more discontinuation, diarrhea andfatigue, but less hypertension than bevacizumab

• The unusually low OS in ICON 6 might possibly be related to anunusually low PPS

A Phase 3, Randomized, Double-blind Trial of Weekly PaclitaxelPlus the Angiopoietin 1 and 2

Inhibitor, Trebananib, or Placeboin Women with Recurrent

Ovarian Cancer:Ovarian Cancer:

TRINOVA-1Bradley J. Monk, Andrés Poveda, Ignace Vergote,

Francesco Raspagliesi, Keiichi Fujiwara, Duk-Soo Bae,Ana Oaknin, Lynn Navale, Douglas J. Warner, Amit M. Oza

Presented by Monk BJ at European Cancer CongressEuropean Journal of Cancer 49; suppl 3, Sept 2013 LBA 41

Angiopoietin Axis –Ang1 and Ang2 Interact With Tie2 Receptorto Mediate Vascular Remodeling

Ang1 stabilizes endothelial junctionsand increases pericyte coverage1,2

“Vessel quality”

Ang-1Ang1

Ang2 promotes endothelial sprouting andincreases blood vessel density1,2,3

“Vessel quantity”

Ang2

1. 1. Augustin HG, et al. Nat Rev Mol Cell Bio. 2009;10:165‒177.2. 2. Falcon BL, et al. Am J Pathol. 2009;175:2159‒2170.3. 3. Scharpfenecker M, et al. J Cell Sci. 2005;118:771‒780.4. 4. Sallinen H, et al. Int J Gynecol Cancer. 2010;20:498‒1505.

NormalVessels

Tie2

Angiopoietins also regulate lymphangiogenesis1

Ang1 and Ang2 levels are elevated in patients with ovarian carcinoma4

AbnormalVessels

Tie2


TRINOVA-1 Trial Design

Recurrent EOC

•≤ 3 prior anticancerregimens

•Evaluable ormeasurable disease

•GOG Performance Treat to

Treat toPD/toxicity

Weekly Paclitaxel+

Weekly Paclitaxel+

Placebo

R

1:1

EOC = epithelial ovarian cancer including primary peritoneal, or fallopian tube cancer; PD = progressive disease

Stratification factors

•Platinum-free interval (PFI) (≤ 6 vs. > 6 months)•Measurable disease (Yes/No)•Region (North America, Western Europe/Australia, Rest of World)

•GOG PerformanceStatus of 0 or 1

•PFI < 12 months

Treat toPD/toxicity

+Trebananib

1:1

Paclitaxel 80 mg/m2 IV on days 1, 8, 15 Q4W

Trebananib 15 mg/kg IV QW

ClinicalTrials.gov Identifier: NCT01204749


TRINOVA-1 Timeline

March 2013Data Lock

October 1, 2013PFS and InterimOS Presented

Anticipate PrimaryAnticipate Primary

November 2012Closed to Enrollment

November 2010Open to Enrollment

2013

Anticipate PrimaryOS Data

Anticipate PrimaryOS Data

2010 2011 2012 2014

919 Patients from 179 sites in 32 countries were randomized

2014


Demographics and BaselineCharacteristics

Paclitaxel +PlaceboN = 458

Paclitaxel +Trebananib

N = 461

Histologic grade, n (%)Well differentiatedModerately differentiatedPoorly differentiatedUnknown

31 (7)84 (18)

256 (56)87 (19)

24 (5)69 (15)

274 (59)94 (20)

Prior lines of therapy, n (%)*Prior lines of therapy, n (%)*123

172 (38)172 (38)114 (25)

190 (41)174 (38)94 (20)

Platinum-free interval, n (%)†

< 6 months≥ 6 months

245 (53)212 (46)

235 (51)223 (48)

Measureable disease at baseline, n (%) 433 (95) 435 (94)

Region, n (%)North AmericaWestern Europe/AustraliaRest of the world

91 (20)189 (41)178 (39)

93 (20)193 (42)175 (38)

*Three patients had 4 or unknown lines of prior therapy (protocol deviation); †Four patients were “refractory” (protocol deviation)Presented by Monk BJ at European Cancer CongressEuropean Journal of Cancer 49; suppl 3, Sept 2013 LBA 41

Progression-free Survival(Primary Analysis)

Pac + Placebo(n = 458)

Pac + Trebananib(n = 461)

Events, n (%) 361 (79) 310 (67)

Median PFS, months 5.4 7.2

HR = 0.66 (95% CI, 0.57–0.77)P (stratified log rank) < 0.001

Eve

nt-

fre

eP

rob

ab

ility

0.7

0.8

0.9

1.0

Eve

nt-

fre

eP

rob

ab

ility

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Study Month0 3 6 9 12 15 18 21 22

Patients at risk:

461458

356310

176132

10568

5024

2210

142

30

10


Treatment-emergent AEs in≥ 25% of Patients

Patient Incidence, n (%)

Paclitaxel +PlaceboN = 458

Paclitaxel +Trebananib

N = 461

All Grades Grade ≥ 3 All Grades Grade ≥ 3

Any 434 (96) 244 (54) 446 (97) 258 (56)

Localized edema 116 (26) 4 (1) 264 (57) 24 (5)

Nausea 171 (38) 6 (1) 187 (41) 8 (2)Nausea 171 (38) 6 (1) 187 (41) 8 (2)

Alopecia 163 (36) 2 (<1) 154 (33) 0

Diarrhea 122 (27) 13 (3) 136 (30) 11 (2)

Abdominal pain 131 (29) 21 (5) 132 (29) 22 (5)

Asthenia 119 (26) 15 (3) 129 (28) 13 (3)

Fatigue 137 (30) 17 (4) 127 (28) 15 (3)

Vomiting 101 (22) 12 (3) 122 (26) 14 (3)

Constipation 128 (28) 4 (1) 105 (23) 3 (1)

Neutropenia 125 (28) 40 (9) 99 (21) 26 (6)


TRINOVA-1 – Conclusions

TRINOVA-1 met its primary objective of PFS

Trebananib plus paclitaxel significantly prolonged PFS comparedwith placebo plus paclitaxel in recurrent EOC

HR = 0.66 (P < 0.001)HR = 0.66 (P < 0.001)QOL maintained without decrement

Toxicity was characterized by edema, pleural effusion, and ascites


Petronella Witteveen1, Alain Lortholary2, Tanja Fehm3, Andrés Poveda4,

Final overall survival results from AURELIA, anopen-label randomised phase III trial of chemotherapy

with or without bevacizumab for platinum-resistantrecurrent ovarian cancer

Petronella Witteveen1, Alain Lortholary2, Tanja Fehm3, Andrés Poveda4,Alexander Reuss5, Hanne Havsteen6, Francesco Raspagliesi7,Ignace Vergote8, Aristotelis Bamias9, Eric Pujade-Lauraine10

on behalf of the AURELIA investigators

1DGOG and University Medical Center Utrecht, Utrecht, The Netherlands; 2GINECO andCentre Catherine de Sienne, Nantes, France; 3AGO and University Clinic Tübingen,

Tübingen, Germany; 4GEICO and Instituto Valenciano de Oncologia, Valencia, Spain;5AGO and Coordinating Center for Clinical Trials, Marburg, Germany; 6NSGO and HerlevUniversity Hospital, Copenhagen, Denmark; 7MITO and Istituto Nazionale Tumori, Milan,Italy; 8BGOG and University Hospital Leuven, Leuven, Belgium; 9HECOG and University

of Athens, Athens, Greece; 10GINECO and Université Paris Descartes, Paris, France

AURELIA trial design

Platinum-resistant OCa

• ≤2 prior anticancerregimens

• No history of bowelobstruction/abdominalfistula or clinical/radiological evidence of

Treat toPD/toxicity

Treat toPD/toxicity

Investigator’schoice

(without BEV)

Optional BEVmonotherapyd

BEV 15 mg/kg q3wc

+ chemotherapy

Chemotherapy

Rb

1:1

ORR = objective response rate; PD = progressive disease; PFS = progression-free survival;aEpithelial ovarian, primary peritoneal or fallopian tube cancerbStratification factors: selected chemotherapy; prior anti-angiogenic therapy; platinum-free interval (<3 vs 3–6 months)cOr 10 mg/kg q2w. d15 mg/kg q3w, permitted on clear evidence of PD

Primary endpoint: PFS (RECIST v1.0)

Secondary endpoints:

• ORR

• OS (after OS events in 70%)

• Quality of life

• Safety and tolerability

rectosigmoid involvement(without BEV)

Chemotherapy options (investigator’s choice):

• Paclitaxel 80 mg/m2 days 1, 8, 15, & 22 q4w

• Topotecan 4 mg/m2 days 1, 8, & 15 q4w(or 1.25 mg/m2, days 1–5 q3w)

• PLD 40 mg/m2 day 1 q4w

Primary PFS analysis

CT(N=182)

BEV + CT(N=179)

Events, n (%) 166 (91) 135 (75)

Median PFS, months(95% CI)

3.4(2.2‒3.7)

6.7(5.7‒7.9)

HR (unadjusted)(95% CI)

0.48(0.38‒0.60)p<0.001a

1.0

0.8

0.6

Estim

ate

dpro

babili

ty

Data cut-off: 14 November 2011. Median duration of follow-up: 13.9 months (CT arm) vs 13.0 months (BEV + CT arm)HR = hazard ratioa2-sided log-rank, unadjusted

0.4

0.2

0

Estim

ate

dpro

babili

ty

0 6 12 18 24

Time (months)182 37 8 1 0

179 88 18 1 0

CT

BEV + CT

No. at risk:

93

14020

49

1

4

0

1

3.4 6.7

Paclitaxel cohort: OSO

ve

rall

su

rviv

al(%

)

75

50

100CT

(N=55)BEV + CT

(N=60)

Events, n (%) 41 (75) 36 (60)

Median OS,months (95% CI)

13.2(8.2‒19.7)

22.4(16.7‒26.7)


0.65(0.42‒1.02)

Ove

rall

su

rviv

al(%

)

50

25

00 6 12 18 24 30 36 42

CT

BEV + CT

No. at risk:

55 40 32 22 13 3 0

60 52 43 34 19 4 1

Time (months)

• Interpretation of OS is complicated by planned crossover andthe lack of information on post-progression therapy

• Exploratory subgroup analyses suggested:

– Generally consistent effects on OS

Conclusions

– Generally consistent effects on OS

– More pronounced OS treatment effect in the weeklypaclitaxel subgroup

OS: ITT population

CT(N=182)

BEV + CT(N=179)

Events, n (%) 136 (75) 128 (72)

Median OS,months (95% CI)

13.3(11.9‒16.4)

16.6(13.7‒19.0)


0.85(0.66‒1.08)p=0.174a

100

75

50

Ove

rall

su

rviv

al(%

)

Data cut-off: 25 January 2013. Median duration of follow-up: 27.4 months in both armsITT = intent to treata2-sided log-rank, unadjusted

CT

BEV + CT

No. at risk:

182 130 98 63 29 12 1 0

179 148 106 75 39 13 1 0

0 6 12 18 24 30 36 42

Time (months)

25

0

Ove

rall

su

rviv

al(%

)

samo forome post-esmo · cediranib plus platinum-based ct followed by maintainance cediranib...

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