COOL - Community in Oncology On Lung Cancer www.esanum.it/cool

1. 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

2. 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

3. Maintenenance therapy more effective in
NSCLC with high risk of progression
OSprobability
1.0
0.8
0.6
0.4
0.2
0
0 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
0
0 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

4. SATURN: OS according to EGFR
mutation status
0 3 6 9 12 15 18 21 24 27 30 33 36
OSprobability
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=0.0243
HR=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

5. Maintenance treatment of
Gemcitabine +BSC vs. BSC
Gemcitabine +
Carboplatin X
4 cycles
R
A
N
D
O
M
I
Z
E
Gemcitabine q 21
days + BSC
N= 128
BSC
N= 127
CR, PR
SD
Off study
PD
Randomization factors:
• PS status
• Stage
• Best tumour repsonse
Primary Endpoint OS
Belani et al, ASCO 2010
~60% of PS2 Patients

6. 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
0.0
Gemcitabine 8.0 mos.
BSC 9.3 mos.
HR=0.97 (95% CI:0.72, 1.30)
P =0.838

7. 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
Probability
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.
Probability
Pemetrexed
Placebo
Immediate Docetaxel
Delayed Docetaxel

8. Maintenance Erlotinib – SATURN OS:
Curves Separate Late and Stay Separated for
Many Months
1.0
0.8
0.6
0.4
0.2
0
6 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
Probability