CORRADO BONI - Cipomo · CORRADO BONI . Colon Cancer: setting the scene . P=0.0001 OS improves with...

La valorizzazione dei benefici per il paziente con

l’introduzione dei nuovi farmaci: Carcinoma del Colon

CORRADO BONI

Colon Cancer: setting the scene

P=0.0001

OS improves with the exposure to 3 cytotoxics

Grothey et al. JCO ‘05

1st line

2nd line

3rd line

The proportion of patients

receiving therapy diminishes

with subsequent lines

Biologici nel MCRC

Anti Angiogenici

1° Linea

Mantenimento

Beyond progression

2° Linea e oltre

Anti EGFR

1° Linea

2° Linea e oltre

Anti Angiogenici

Antiangiogenic treatment in mCRC

Arnold & Tabernero, J Oncopathol 2013; 3 (Sept): 111-19

Prima Linea

Treatment duration and PFS in AVF2107 vs NO16966

Treatment duration

PFS

Placebo

Bevacizumab

Placebo Bevacizumab

Placebo

Bevacizumab

Placebo

Bevacizumab

AV

F2

10

71

N

O1

69

66

2

Treatment duration

PFS

Months

+ 2.8

+ 4.4

+/- 0

+ 1.4

Months

0 2 4 6 8 10 12

0 2 4 6 8 10 12

NO16966 median treatment duration:

• Bevacizumab + XELOX

• Placebo + XELOX

• Bevacizumab + FOLFOX-4

• Placebo + FOLFOX-4

6.1 m

5.4 m

6.3 m

6.0 m

NO16966: Fluoropirimidina + Oxa + Beva FOLFOX/XELOX vs FOLFOX/XELOX+Beva in first line:

NO16966

Saltz et al, ASCO GI ‘07

ITT: HR: 0.83, p=0.0023

On-treatment HR: 0.63, p<0.0001

On-treatment PFS: 10.4 vs 7.9 months

∆ +2.5

Efficacy of FOLFIRI + Bevacizumab in the treatment of 1st line mCRC

FOLFIRI + bevacizumab

Hellenic COG

Pectasides

20121

FNCLCC/

ACCORD

Ducreux

20132

TRIBE

Falcone 20133

FIRE-3*

20134

n 142 73 256 295

ORR (ITT), % 40.1 59 53.0 58

PFS, mo 10.8 9 9.7 10.3

OS, mo 25.3 23 25.8 25.0

1. Pectasides D, et al BMC Cancer 2012;12:271–281; 2. Ducreux M, et al. EJC 201;49:1236–1245;

3. Falcone A, et al. ASCO 2013 (Abstract No. 3505);

4. Heinemann V, et al. ASCO 2013 (Abstract No. LBA3506

* Pts with KRAS wt tumors

FOLFIRI

122 pts

FOLFOXIRI

122 pts P value

Confirmed RR 34% 60% <0.0001

R0 surgery (all) 6% 15% 0.033

R0 surgery (liver) 12% 36% 0.017

mPFS (mos) 6.9 9.9 0.0009

mOS (mos) 16.7 23.6 0.042

Falcone A et al. JCO 2007 and ASCO 2007

FOLFOXIRI vs FOLFIRI: Activity and Efficacy

TRIBE trial

R 1:1

508 pts1st line

unresectable

mCRC pts

stratified by

ü center

ü PS 0/1-2

ü adjuvant CT

FOLFIRI + bev*

FOLFOXIRI + bev*

• Bev 5 mg/kg ev g1

• Irinotecan 180 mg/sqm ev g1

• L-LED 200 mg/sqm ev g1

• 5-FU 400 mg/sqm ev g1 bolus

• 5-FU 2400 mg/sqm ev gg1 3

• Bev 5 mg/kg ev g1

• Irinotecan 165 mg/sqm ev g1

• Oxaliplatin 85 mg/sqm ev g1

• L-LED 200 mg/sqm ev g1

• 5-FU 3200 mg/sqm ev gg1 3

*both repeated every 2 wks for a max of 12 cycles followed by maintenance with 5FU/bev until PD

Primary endpoint: PFS

Loupakis et al. ASCO-GI 2013

Median follow up: 26.6 mos

FOLFIRI + bev: N = 256 / Progressed = 225 FOLFOXIRI + bev: N = 252 / Progressed = 199

FOLFIRI + bev, median PFS : 9.7 mos FOLFOXIRI + bev, median PFS : 12.2 mos

Unstratified HR: 0.73 [0.60-0.88]

p = 0.0012

Stratified HR: 0.71 [0.59-0.86] p=0.0006

Primary endpoint: PFS – ITT population P

rog

ressio

n-f

ree s

urv

ival pro

babili

ty

F-up time (months)

FOLFIRI + bev

FOLFOXIRI + bev

PD-free rate at 2 years:

11.4% vs 20.3%


Secondary endpoint: Response Rate (ITT population)

Best Response, %

FOLFIRI + bev

N = 256

FOLFOXIRI + bev

N = 252 p

Complete Response 3% 4%

Partial Response 50% 61%

Response Rate 53% 65% 0.006

Stable Disease 32% 24%

Progressive

Disease 5% 2%

Not Assessed 10% 9%


Secondary endpoint: OS (preliminary) – ITT population

FOLFIRI/bev 256 233 216 172 109 69 36 15 5 0

FOLFOXIRI/bev 252 234 205 175 119 70 35 15 4 0

Ove

rall

su

rviv

al

pro

bab

ilit

y

F-up time (months)

FOLFIRI + bev

FOLFOXIRI + bev

Median follow up: 32.3 mos

FOLFIRI + bev: N = 256 / Died = 155

FOLFOXIRI + bev: N = 252 / Died = 131

FOLFIRI + bev, median OS : 25.8 mos

FOLFOXIRI + bev, median OS : 31.0 mos

Unstratified HR: 0.83 [0.66-1.05]

p=0.125

Stratified HR: 0.79 [0.63-1.00]

p=0.054

AVEX - Study design

Previously untreated mCRC, age >70 years N=280

Capecitabine 1000 mg/m2 b.i.d. days 1–14, q21d

Capecitabine 1000 mg/m2 b.i.d. days 1–14, q21d

+ Bevacizumab 7.5 mg/kg day 1, q21d

Randomize 1:1

Stratification factors:

– ECOG PS (0–1 vs 2)

– Geographic region

• Key inclusion criteria

– ECOG PS 0–2

– Prior adjuvant chemotherapy allowed if completed >6 month before inclusion

– Not optimal candidates for a combination chemotherapy with irinotecan or oxaliplatin

• Key exclusion criteria

– Prior chemotherapy for mCRC or prior adjuvant anti-VEGF treatment

– Clinically significant cardiovascular disease

– Current or recent use of aspirin (>325 mg/day) or other NSAID

– Use of full-dose anticoagulants or thrombolytic agents Cunningham ASCO-GI 2013

Progression-free survival P

FS

estim

ate

1.0

0.8

0.6

0.4

0.2

0.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40

Number at risk

Cape + BEV

Cape

140 121 99 80 68 55 41 28 23 16 13 9 8 3 2 2 2 2 1 0 0

140 109 82 56 38 25 13 9 6 4 4 2 1 1 1 1 1 1 1 1 0

Time (months)

Cape + BEV (n=140)

Cape (n=140)

5.1 mo 9.1 mo

HR=0.53 (95% CI: 0.41–0.69)

p < 0.001

ITT population. 113 PFS events in the Cape + BEV arm; 127 PFS events in the Cape arm. CI = confidence interval; PFS = progression-free survival

Cunningham ASCO-GI 2013

Overall survival

1.0

0.8

0.6

0.4

0.2

0.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46

Number at risk Cape + BEV

Cape

140 126 120 106 95 89 81 67 60 51 44 40 34 24 16 15 12 10 8 6 5 4

140 120 108 94 85 73 62 57 49 37 33 23 19 13 11 10 9 7 6 5 5 3

OS

estim

ate

Time (months)

2

1

0

0

16.8 mo 20.7 mo

HR=0.79 (95% CI: 0.57–1.09)

p = 0.182

Cape + BEV (n=140)

Cape (n=140)

ITT population. 75 OS events in each treatment arm. Cunningham ASCO-GI 2013

Mantenimento

Bevacizumab-based trials focussing on maintenance or bev-based sequence

Study Regimen PFS

(months)

OS

(months)

MACRO1 CAPOX + Bev 10.4 23.4

CAIRO-32 Chemo + Bev 11.8 19.8 + 4.5 ?

SAKK 41/063 Chemo + Bev 9.5 25.1

TML4 Chemo + Bev 23.9 1. Tabernero, et al. ASCO 2010 (Abstract No. 3501); 2. Koopmann M, et al. ASCO 2013 (Abstract No. 3502);

3. Koeberle D, et al. ASCO 2013 (Abstract No. 3503); 4. Bennouna J, et al. Lancet Oncol 2013;14:29–37

Randomized studies: results from most efficacious treatment arms

Xelox+ Bev

N=239 Xelox+ Bev

x 6 cycles Bev

N=241

OS PFS

MACRO conclusions

Although the MACRO study did not meet its primary

endpoint of noninferiority, the results suggest that single-

agent bevacizumab after six cycles of XELOX plus

bevacizumab may be a potential alternative to continued

XELOX plus bevacizumab for patients with mCRC.

Phase III CAIRO-3 Trial: Maintenance Capecitabine + Bev vs Obs in mCRC

Primary endpoint: PFS2

Time from randomization to progression upon reintroduction of CAPOX-B

PFS2 considered equal to PFS1 in patients who do not receive CAPOX-B again

Median follow-up: 40 mos

Patients with

mCRC and SD or

better after 6

cycles CAPOX-B,

WHO PS 0-1

(N = 558)

Observation

(n = 279)

Capecitabine +

Bevacizumab

(n = 279)

PD

Reintroduce

CAPOX-B PD

PFS1 PFS2

OR

Any treatment,

including

CAPOX-B

PD

TT2PD

Koopman M, et al. ASCO 2013. Abstract 3502.

CAIRO-3 Trial of Maint Capecitabine + Bev vs Obs in mCRC: TT2PD and OS Results

Koopman M, et al. ASCO 2013. Abstract 3502. Used with permission.

OS

Pro

ba

bil

ity

Maintenance treatment with capecitabine + bev after 6 cycles CAPOX-B significantly prolongs TT2PD and OS

(95% CI: 13.6-16.4) (95% CI: 18.0-21.9) (95% CI: 0.55-0.81)

TT

2P

D P

rob

ab

ilit

y

Mos

1.0

0.8

0.6

0.4

0.2

0

0 6 12 18 24 30 36

Observation Maintenance Stratified HR P value

15.0 19.8 0.67 < .00001

Adjusted HR: 0.63; p < .001

Median TT2PD, Mos

Maintenance

Observation

Mos

1.0

0.8

0.6

0.4

0.2

0

0 6 12 18 24 30 36

Observation Maintenance Stratified HR P value

18.2 21.7 0.87

.156

Adjusted HR: 0.80; p = .035 (preliminary survival analysis)

Median OS, Mos

Maintenance

Observation

(95% CI: 16.3-20.8) (95% CI: 19.4-24.0) (95% CI: 0.71-1.06)

Phase III SAKK 41/06 Study: Bev vs No Bev After First-line Chemo-Bev in mCRC

Primary endpoint: TTP (measured by CT q6w until PD)

Secondary endpoints: PFS, TTNT, OS, bev-related toxicity,

treatment costs

Patients with mCRC who

received first-line chemo

+ bev for 4-6 mos, have

≥ SD, WHO PS 0-1

(N = 262)

Bev 7.5 mg/kg q3w

(n = 131)

No antitumor treatment

(n = 131)

PD

Koeberle D, et al. ASCO 2013. Abstract 3503. Used with permission.

SAKK 41/06 Study of Bev vs No Bev After First-line Chemo-Bev in mCRC: PFS


Pro

po

rtio

n W

ith

ou

t P

rog

res

sio

n/D

ea

th

1.0

0.8

0.6

0.4

0.2

0

0 6 12 18 24 30 36 42 48

Mos

Bev No bev

No. of events

Median, mos (95% CI)

HR 95% CI

Difference

Bev

125

9.5 (8.6-10.2)

No Bev

124

8.5 (8.0-8.9)

0.75 (0.58-0.96)

p = .021

Pts at Risk, n Bev No bev

131 131

40 18

13 8

6 7

6 4

5 1

3 1

2 0

1 0

54

122 116

SAKK 41/06 Study of Bev vs No Bev After First-line Chemo-Bev in mCRC: OS


Pro

po

rtio

n S

urv

ivin

g

1.0

0.8

0.6

0.4

0.2

0

0 6 12 18 24 30 36 42 48

Mos

Bev No bev

Events, n

Median, mos (95% CI)

HR (95% CI)

Difference

Bev

84

25.1 (22-28.9)

No Bev

84

22.8 (20.3-26.1)

0.83 (0.61-1.12)

p = .218

Pts at Risk, n Bev No bev

131 131

115 107

86 76

52 44

33 25

22 13

10 6

3 1

1 1

54

130 131

60

0 1

Summary

Non-inferiority could not be demonstrated

The difference in median TTP between BEV continuation

versus no treatment after randomization is 5 weeks

Overall survival in both arms is not significantly different

Utility of BEV continuation needs to be balanced

with significantly higher treatment costs

Awaited data from randomized fase III trials

Beyond Progression

Background: Beva Beyond 1st PD “BRiTE trial “

Survival after 1st PD

Grothey et al. ASCO 2007 and JCO 2008

CT+Beva

CT No Treat.

RETROSPECTIVE!!

BEV + standard first-line CT (either oxaliplatin or irinotecan-based) (n=820)

Randomise 1:1

Standard second-line CT (oxaliplatin or irinotecan-based)

until PD

BEV (2.5 mg/kg/wk) + standard second-line CT (oxaliplatin or irinotecan-based)

until PD

PD

ML18147 study design (phase III)

CT switch:

Oxaliplatin → Irinotecan

Irinotecan → Oxaliplatin

Study conducted in 220 centres in Europe and Saudi Arabia

Primary endpoint • Overall survival (OS) from randomisation

Secondary endpoints • Progression-free survival (PFS)

• Best overall response rate

• Safety

Stratification factors • First-line CT (oxaliplatin-based, irinotecan-based)

• First-line PFS (≤9 months, >9 months)

• Time from last BEV dose (≤42 days, >42 days)

• ECOG PS at baseline (0/1, 2)

Arnold et al, ASCO 2012

PFS: ITT population P

FS

estim

ate

Time (months)

1.0

0.8

0.6

0.4

0.2

0

0 6 12 18 24 30 36 42

CT (n=410) BEV + CT (n=409)

4.1 mo 5.7 mo

Unstratifieda HR: 0.68 (95% CI: (0.59–0.78) p<0.0001 (log-rank test)

Stratifiedb HR: 0.67 (95% CI: 0.58–0.78)

p<0.0001 (log-rank test)


OS: ITT population O

S e

stim

ate

Time (months)

1.0

0.8

0.6

0.4

0.2

0

0 6 12 18 24 30 36 42 48

CT (n=410) BEV + CT (n=409)

9.8 mo 11.2 mo

Unstratifieda HR: 0.81 (95% CI: 0.69–0.94)

p=0.0062 (log-rank test)

Stratifiedb HR: 0.83 (95% CI: 0.71–0.97)

p=0.0211 (log-rank test)

Median follow-up: CT, 9.6 months (range 0–45.5); BEV + CT, 11.1 months (range 0.3–44.0)


∆ +1.4

BEBYP: Study Design

B. Second-line CT§+ BV

I-line CT * + BV Stratification

‐ Center

‐ PS 0/1-2

‐ CT-free interval

(> vs ≤ 3 mos)

‐ II-line CT

R A N D O M

• FOLFIRI • FOLFOX • FOLFOXIRI • Fluoropyrimidine mono-tx

* • FOLFIRI

• mFOLFOX-6

§

A. Second-line CT§

• Primary end-point: PFS • Accrual stopped prematurely: 184 pts for ITT

Masi et al. ESMO 2012 Salvatore et al. AIOM 2012

CT (85 events) median PFS = 4.97 mos

CT+ B (87 events) median PFS = 6.77 mos

HR=0.65 (95%CI 0.48-0.89)

p=0.0062

Median follow up 18.0 mos

Primary Objective - PFS

Masi et al. ESMO 2012 Salvatore et al. AIOM 2012

Seconda Linea

Giantonio, et al. JCO 2007

Bevacizumab: 2nd line superior PFS + OS with FOLFOX

PF

S e

sti

ma

te

1.0

0.8

0.6

0.4

0.2

0

Months

0 2 4 6 8 10 12 14 16 18 20 22 24 26

FOLFOX4 + Avastin

FOLFOX4

Ove

rall

su

rviv

al

es

tim

ate

1.0

0.8

0.6

0.4

0.2

0

Months

FOLFOX4 + Avastin

FOLFOX4

0 3 6 9 12 15 18 21 24 27 30 33 36

7.3 4.7 12.9 10.8

OS

10.8 vs 12.9 months

HR=0.75 (p=0.0011)

PFS

4.7 vs 7.3 months

HR=0.61 (p<0.0001)

Van Cutsem et al, JCO 2012

VELOUR: Study Design


FOLFIRI vs FOLFIRI+Aflibercept VELOUR study: OS

∆ +1.4


Secondary Objectives – PFS and RR

C. J. Allegra et al. J Clin Oncol 30, 2012 (suppl; abstr 3505)

VELOUR-Trial: Results by prior Bev

FOLFIRI

(n=614)

Aflibercept/FOLFIRI

(n=612)

HR

OS

no BEV

(n=853) 12.4 13.9

0.788

prior BEV

(n=373) 11.7 12.5

0.862

PFS

no BEV 5.4 6.9

0.797

Prior BEV 3.9 6.7 0.661

RR

no BEV

Prior BEV

12.4%

8.4 %

23.3%

11.7 %

Regorafenib *

Placebo

• mCRC pts

• Progressed

after standard

therapies

R 2:1

* 160 mg per os once daily,

3 weeks on, one week off.

Primary end-point: OS

N= 690

CORRECT trial – Study design

Stratification by

ü Prior anti-VEGF tx

ü Time to mts disease

ü Geographical region

Van Cutsem et al. ASCO 2012

CORRECT trial - PFS


Correct trial: Primary endpoint OS


∆ +1.4

Anti EGFR

OS nello Studio CRYSTAL in paz. non selezionati per KRAS

Popolazione dello studio CRYSTAL

Time (months)

54 42 48

Cetuximab + FOLFIRI (n=599)

FOLFIRI (n=599)

0.0

0.2

0.4

0.6

0.8

1.0

18 0 6 12 24 30 36

OS

esti

ma

te

HR=0.878

p=0.0419

19.9

18.6

Van Cutsem E, et al. J Clin Oncol 2011;29:2011–2019

CRYSTAL Popolazione KRAS wt

Time (months)

54 42 48

23.5

20.0

0.0

0.2

0.4

0.6

0.8

1.0

18 0 6 12 24 30 36

OS

es

tim

ate

Cetuximab + FOLFIRI (n=316)

FOLFIRI (n=350)

HR=0.796

p=0.0093

Van Cutsem E, et al. J Clin Oncol 2011;29:2011–2019

OS nello Studio CRYSTAL in pazienti KRAS WT

Douillard JY et al, JCO 2010

Enrolled pts: 1183

Randomization stratification:

• ECOG performance status: 0 - 1 vs 2

• Geographic region: Western Europe, Canada, and Australia vs rest of the world

Primary endpoint: PFS

Disease assessment every 8 weeks

The PRIME Study

Douillard JY et al, JCO 2010

The PRIME Study: PFS in WT KRAS pts

Oliner KS et al , ASCO 2013 #3511

KRAS wt exon 2 (60%) KRAS mut exon 2 (40%)

KRAS or NRAS mut

(17%) BRAFmut (8%)

The PRIME Study: KRAS, NRAS and BRAF mutations

Summary of RAS subgroup analyses

RAS wt

~50%

RAS mt

~50%

Stintzing S, et al. ECC 2013 (Abstract No. LBA17);

Tejpar S, et al. ASCO GI 2014 (Abstract No. LBA444); Douillard J-Y, et al. N Engl J Med 2013;369:1023–1034

RAS mutations in mCRC

Phase III Study PRIME (FOLFOX + Panitumumab vs FOLFOX); patients evaluated 90%

Oliner et al, Abstract 3511, ASCO 2013

FOLFOX + Pan

(No. 320)

FOLFOX

(No. 321)

HR p

Douillard, JCO 2010

KRAS wt 23.9

(100%)

19.7 (100%)

0.83 0.72

RAS wt OS (months) 26.0 (81%)

20.2 (79%)

0.78 0.04

RAS m OS (months) 15.6 (85%)

19.2 (86%)

1.25 0.04

RAS/BRAF wt (months) 28.3 (71%)

20.9 (68%)

0.74 0.02

BRAF m (months) 10.5

(8%)

9.2

(9%)

0.90 0.76

PICCOLO (Panitumumab+CPT vs CPT II line): OS according to KRAS/BRAF status

Seymour et al. ASCO ‘11

Schwartzberg, JCO 2014

PEAK: Overall Survival in KRAS Wild Type

Schwartzberg, JCO 2014

PEAK: Overall Survival in all RAS Wild Type

FIRE-3: Head-to-head cetuximab + FOLFIRI vs bevacizumab + FOLFIRI in 1st line mCRC

Heinemann V, et al. ASCO 2013 (Abstract No. LBA3506); Modest D, et al. WCGC 2013 (Abstract No. O-0029);

Stintzing S, et al. ECC 2013 (Abstract No. LBA17); Stintzing S, et al. Ann Oncol 2012;23:1693–1699

Patients with untreated

KRAS (exon 2) wt mCRC

N=592

Open-label, randomized, multicenter Phase III IST

R

Cetuximab + FOLFIRI

Bevacizumab + FOLFIRI

n=297

n=295

● Primary endpoint: ORR

● Secondary endpoints: PFS, OS, TFS, DpR, secondary resection rate, safety

● Amendment in October 2008 to include only patients with KRAS (exon 2)

wt mCRC

● 113 patients with KRAS (exon 2) mt mCRC were enrolled before the amendment

DpR: depth of response; TFS: time to failure of strategy;

IST: investigator-sponsored trial

Primary analysis: Evaluation of ORR (ITT)

ORR

FOLFIRI +

cetuximab

FOLFIRI +

bevacizumab Odds ratio p

% 95% CI % 95% CI

ITT population

(N=592) 62.0 56.2–67.5 58.0 52.1–63.7

1.18

0.85–1.64 0.183

p=one-sided Fisher‘s exact test Heinemann V, et al. ASCO 2013 (Abstract No. LBA3506)

[TITLE]

Presented By Sebastian Stintzing, MD at 2013 ASCO Annual Meeting

Subsequent anticancer therapy

FOLFIRI + cetuximab

n=297

FOLFIRI + bevacizumab

n=295 p

Any 2nd line therapy, % 65.7 61.7 0.347

2nd line bevacizumab, % 48.2 17.6

2nd line anti-EGFR, % 14.4 42.9

p=two-sided Fisher‘s exact test Heinemann V, et al. ASCO 2013 (Abstract No. LBA3506)

Head-to-head trials of targeted agents in 1st line mCRC

1. Heinemann V, et al. ASCO 2013 (Abstract No. LBA3506); 2. Naughton MJ, et al. ASCO 2013 (Abstract No. 3611); 3. NCT00265850; 4. Schwartzberg LS, et al. ASCO GI 2013 (Abstract No. 446); 5. Schwartzberg LS, et al. ASCO 2013 (Abstract No. 3631)

FIRE-31

CALGB 804052,3

PEAK4,5

Patients with untreated KRAS wt mCRC

N=592 R

Cetuximab + FOLFIRI

Bev + FOLFIRI


N~1200 (after trial modification)

Cetuximab + FOLFOX/FOLFIRI

Bev + FOLFOX/FOLFIRI

Bev + cetuximab + FOLFOX/FOLFIRI*

*Arm closed to accrual as of 09/10/2009


N=285 R

Pani + mFOLFOX6

Bev + mFOLFOX6

R

Pro

po

rtio

n P

rog

ressio

n F

ree

6 12 21 15 33 39

4.0 mos

16.4% RR

2.6 mos

4.2% RR

Mos

HR: 0.692 (95% CI: 0.617-0.776;

stratified log-rank P ≤ .0001)

Irinotecan + cetuximab (n = 648)

Irinotecan alone (n = 650)

Phase III EPIC Trial: Irinotecan ± Cetuximab in 2nd-line mCRC After Ox-Fp CT Failure

NO DIFFERENCE OS But crossover allowed

Sobrero AF, et al. J Clin Oncol. 2008;26:2311-2319.

1.0

0.8

0.6

0.4

0 0

0.2

3 9 18 30 24 27 36

∆ +1.4

● July 2009–June 2013: 340 patients enrolled for 1st line therapy

● As of January 31 2014, 180 patients had progressed and were randomized to receive ongoing 2nd line therapy

CAPRI GOIM trial: Investigating the use of anti-EGFR therapy in multiple lines

Ciardiello F, et al. ECC 2013 (Abstract No. LBA31)

Primary endpoints

1st line treatment: PFS1 2nd line treatment: PFS2

2nd line

1st line

KRAS wt (exon 2) mCRC

(local pathology laboratory

assessment for KRAS codons 12 and

13) PFS2 PFS1

Cetuximab +

FOLFIRI

Treat

until

PD or

toxicity

Treat

until

PD or

toxicity

R

Cetuximab +

mFOLFOX4

mFOLFOX4

Retrospective analysis of biomarkers at diagnosis

Clinical activity of

cetuximab + FOLFIRI

Evaluated for

22 gene

mutation

analysis

(n=182)

KRAS/NRAS wt

(n=124)

KRAS/NRAS mt

(n=58)

Complete response, n (%) 12 (6.6) 8 (6.4) 4 (6.9)

Partial response, n (%) 92 (50.5) 69 (55.6) 23 (39.7)

Stable disease, n (%) 61 (33.5) 35 (28.2) 26 (44.8)

Progressive disease, n

(%) 17 (9.3) 12 (9.7)

5 (8.6)

ORR, n (%)

[95% CI]

104 (57.1)

[52.0–66.4]

77 (62.0)

[55.5–74.6]

27 (46.6)

[39.9–57.5]

Median PFS, months

[95% CI]

9.8

[8.7–11.5]

11.1

[9.2–12.8]

8.9

[7.4–9.6]

CAPRI GOIM: 1st line efficacy data (KRAS/NRAS wt vs mt)

Ciardiello F, et al. ECC 2013 (Abstract No. LBA31)

Un rilevante progresso derivante da: - disponibilità di nuovi agenti biologici - continuo miglioramento delle conoscenze della biologia del tumore - miglioramento della strategia terapeutica Una grande distanza percorsa con piccoli passi

Ribero D et al. Cancer ‘07

Retrospective analysis 105 pts 5FU/OX +/- Beva

<25% residual viable cells

FU/OX: 23% FU/OX+Beva 45% P=0.02

CORRADO BONI - Cipomo · CORRADO BONI . Colon Cancer: setting the scene . P=0.0001 OS improves with...

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