Should we give maintenance therapy in NSCLC?

Factors influencing the decision

• Patient preference• Risk of progression

– Response to front-line chemotherapy– EGFR status

• Performance status• Age

Maintenance therapy paradigm

First-line platinum-based chemotherapy x 4-6 cycles

No Progression-PS 0-1

In favor of therapyRefuse of any therapy

Prevent PS deterioration: strict

FU (q 4-6 weeks)

Maintenance therapy

Maintenenance therapy more effective in NSCLC with high risk of progression

OS

pro

bab

ilit

y

1.0

0.8

0.6

0.4

0.2

00 3 6 9 12 15 18 21 24 27 30 33 36

Time (months)

9.6 11.9

1.0

0.8

0.6

0.4

0.2

00 3 6 9 12 15 18 21 24 27 30 33 36

Time (months)

12.0 12.5

Log-rank p=0.0019

HR=0.72 (0.59–0.89)

Erlotinib (n=252)

Placebo (n=235)

Log-rank p=0.6181

HR=0.94 (0.74–1.20)

Erlotinib (n=184)

Placebo (n=210)

SD CR/PR

*OS is measured from time of randomisation into the maintenance phase

SATURN: OS according to EGFR mutation status

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

OS

pro

bab

ilit

y

1.0

0.8

0.6

0.4

0.2

0

Time (months)

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

1.0

0.8

0.6

0.4

0.2

0

Time (months)

EGFR mutation+ EGFR wild-type

Log-rank p=0.6810 HR=0.83 (0.34–2.02)

Erlotinib (n=199)

Placebo (n=189)

Erlotinib (n=22)

Placebo (n=27)*

Log-rank p=0.0243HR=0.77 (0.61–0.97)

*Note that 67% of patients with EGFR mutation+ disease in the placebo arm received a second-line EGFR TKI

Maintenance treatment of Gemcitabine +BSC vs. BSC

Gemcitabine +

Carboplatin X

4 cycles

RANDOMIZE

Gemcitabine q 21 days + BSC

N= 128

BSCN= 127

CR, PRSD

Off study

PD

Randomization factors:• PS status

• Stage

• Best tumour repsonse

Primary Endpoint OS

Belani et al, ASCO 2010

~60% of PS2 Patients

Lack of survival benefit with maintenance gemcitabine in PS 2 patients

Overall Survival (months)

0 6 12 18 24 30 36 42 48 54 60

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0Gemcitabine 8.0 mos.

BSC 9.3 mos.

HR=0.97 (95% CI:0.72, 1.30)P =0.838

Maintenance Chemotherapy – OS:Curves Separate Early and Come Together

by 20 Months

0.8

1

0.6

0.4

0.2

0

Placebo: 10.18 mos(95% CI: 8.57-13.17)

Pemetrexed: 13.01 mos(95% CI: 11.40-14.42)

0.8

1

0.6

0.4

0.2

0

Months 55% censored

OS HR = 0.798(95% CI: 0.63-1.01)

0 3 6 9 12 15 18 21 24 27 30 0 4 8 12 16 20 24 28 32 36 40 44 48 52

Pro

bab

ility

Immediate D(N = 153)

Delayed D(N = 156)

Median OS, months(95% CI)

12.3 9.7

12-month survival, % (95% CI)

51.1% 43.5

Months

Pemetrexed vs. Placebo Docetaxel vs. Placebo

Ciuleanu T et al. The Lancet 2009;374(9699):1432-1440. Fidias PM, et al. J Clin Oncol. 2009;27(4):591-598.

Pro

bab

ility

Pemetrexed Placebo

Immediate Docetaxel Delayed Docetaxel

Maintenance Erlotinib – SATURN OS:Curves Separate Late and Stay Separated for

Many Months

1.0

0.8

0.6

0.4

0.2

06 12 18 24 30 33 363 9 15 21 270

Erlotinib (N = 438)Placebo (N = 451)

Months

HR = 0.81 (95% CI: 0.70-0.95);Log-rank p = 0.0088

Pro

bab

ility