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2

Comparison of Overall Survival versus BSC in 2nd line NSCLC

JMEI

HR (Alimta vs. historical BSC) = 0.55

95% CI : (0.33,0.90)

TAX317

HR (Docetaxel vs. BSC) = 0.56

95% CI : (0.35,0.88)

3

Post Study Crossover Chemotherapy

Time varying covariate analysis

Compares Alimta to docetaxel within groups that have similar post study chemo

– Estimates effect of post study chemotherapy

Among patients with no post study chemo

– Alimta to docetaxel HR = 0.84 (0.65, 1.08)

Effect of post study chemo (interaction p=0.10)

– On docetaxel HR = 1.12 (0.81, 1.53)

– On Alimta HR = 1.58 (1.17, 2.12)

4

Weight Loss During TreatmentPercent of Patients with Weight Loss >10%

0.8 % 0.4 %

0%

5%

10%

15%

20%

25%

Alimta T75

TAX 317B JMEI

0%

5%

10%

15%

20%

25%

2 %

T75

25 %

BSC75

p<0.001 p=ns

5

Overall Survival of JBR 21

SUMMARY STATISTICS:Log-Rank test for equality of groups: p=0.0018Wilcoxon test for equality of groups: p=0.0143Survival rate at 12 months for OSI-774: 31% - % C.I. ( 27%, 35%)Survival rate at 12 months for Placebo: 22% - % C.I. ( 16%, 27%)Hazard Ratio of Placebo/OSI-774: 1.309 - 95 % C.I. (1.105, 1.551)

OSI-774 Placebo

Perc

enta

ge

0

20

40

60

80

100

Time (months) # At Risk(OSI-774) # At Risk(Placebo)

0.0488243

10.018859

20.0124

30.000

___ Erlotinib, _____ Placebo *HR 0.71, p <0.0001

Months

31%

22%

* *Adjusted for stratification factors (except centre) AND EGFR status

6

Concern about “Only One Small Historical Study”

No therapy could be non-inferior to docetaxel based on historical comparisons, even if many large studies show equality: So docetaxel would not be non-inferior to itself!

Imprecision of the benefit of docetaxel over best supportive care limits any comparison

Rothmann analysis accounts for imprecision in historical data, even if study is small

If (i) no possibility of comparing with historical studies & (ii) unable to compare with best supportive care: studies will require many thousands of patients

7Time to Progressive Disease

Mo0 181512963 21

1.00

0.75

0.50

0.25

0.00

JMEI: Summary of EfficacyS

urv

iva

l D

istr

ibu

tio

n F

ac

tor

Overall Survival

Mo0 181512963 21

1.00

0.75

0.50

0.25

0.00

Sur

viva

l Dis

trib

utio

n F

unct

ion

0.00

0.25

0.50

0.75

1.00

Post Progression Survival

0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0

STRATA: trt_01=Docetaxel trt_01=LY231514

1.00

0.75

0.50

0.25

0.00

Su

rviv

al

Dis

trib

uti

on

Fa

cto

r

0 15

12.5

10

7.5

52.5

17.5

20

Post Progression Survival

8

Third Line Chemotherapy for the Treatment of NSCLC

TAX 317 Trial

Massarelli et al.

Lung Cancer 2003; 39:55.

700 patients

43 treated 3rd-line

3rd-Line RR: 2.3%

Median Survival: 3.96 mo

9

Study Therapy OR (%) MPFS (mo)

TAX 317B BSC NA 1.6*

JBR 21 BSC+ Placebo

< 1 1.8

TAX 320 V/I 0.8 2.0*

JMEI Alimta 9.1 2.9

JMEI Docetaxel 8.8 2.9

JMBR Alimta 8.9 2.0

* TTPD

Consistency of Secondary Endpoints in 2nd Line NSCLC Trials

10

JMEI: Performance Status 0/1 Patients Alive One Month after Discontinuation without Post-Study

Chemotherapy

Alimta(N=265)

Docetaxel(N=276)

No Post-study Chemotherapy 139 169

0/1 and Alive 1 mo after discontinuation

84 96

11

0.56

Hazard ratio

90%

0.3

8

0.82

Like

lihoo

d ba

sed

on T

ax 3

17Tax 317 90% confidence interval

Likelihood estimate is many times more likely

than the confidence bound

12

0.99

Hazard ratio

95%

0.82 1.20

Like

lihoo

d ba

sed

on J

ME

I95% confidence interval

Likelihood estimate is many times more likely

than the confidence bound