Questions and answers about PARAMOUNT: phase III study of pemetrexed continuation maintenance therapy in advanced non-squamous NSCLC.

1
Questions and answers about PARAMOUNT phase III
study of pemetrexed continuation maintenance
therapy in advanced non-squamous NSCLC.
2
All questions at a glance please click on
question to review
3
PARAMOUNT study design why were 4 cycles of
induction used?
4
Current recommendations for number of cycles in
1st-line treatment
ASCO and ESMO 4 to 6 cycles of a platinum-based
regimen
5
Does PARAMOUNT address the question of pemetrexed
clinical resistance?
6
Pemetrexed continuation maintenance demonstrated
significant PFS benefit for patients9
Investigator-assessed PFS
1.0
Induction 4 cycles of
pemetrexed/cisplatin NOT reflected in the data
endpoints
Progression-free survival ()
0.9
0.8
0.7
Median PFS (95 CI) Pemetrexed 4.1
(3.24.6) Placebo 2.8 (2.63.1)
0.6
0.5
0.4
0.3
0.2
0.1
0
3
9
12
0
6
15
Time (months)
BSCBest Supportive Care
7
PARAMOUNT median PFS according to response to
induction treatment9
8
What is the impact of the PARAMOUNT survival
results on the treatment paradigm in advanced
NSCLC?
9
PARAMOUNT study was powered 9,10,11
for PFS primary end-point
for OS primary end-point
10
Pemetrexed continuation maintenance demonstrated
significant PFS benefit for patients 9
Investigator-assessed PFS
1.0
Induction 4 cycles of
pemetrexed/cisplatin NOT reflected in the data
endpoints
Progression-free survival ()
0.9
0.8
0.7
Median PFS (95 CI) Pemetrexed 4.1
(3.24.6) Placebo 2.8 (2.63.1)
0.6
0.5
0.4
0.3
0.2
0.1
0
3
9
12
0
6
15
Time (months)
BSCBest Supportive Care
11
Pemetrexed/cisplatin followed by pemetrexed
demonstrated a statistically significant OS
benefit in advanced non-squamous NSCLC10
Overall survival from randomisation
1.0
Induction 4 cycles of
pemetrexed/cisplatin NOT reflected in the data
endpoints
Survival probabality ()
0.9
0.8
0.7
0.6
13.9
11.0
HR 0.78
0.5
0.4
0.3
0.2
0.1
0
6
18
24
0
12
30
36
Time from randomisation (months)
BSCBest Supportive Care
12
Pemetrexed/cisplatin followed by pemetrexed
demonstrated a statistically significant OS
benefit in advanced non-squamous NSCLC10
Overall survival from randomisation
1.0
Induction 4 cycles of
pemetrexed/cisplatin NOT reflected in the data
endpoints
Survival probabality ()
0.9
0.8
0.7
0.6
0.5
0.4
32
0.3
0.2
21
0.1
0
6
18
24
0
12
30
36
Time from randomisation (months)
BSCBest Supportive Care
13
PARAMOUNT Final OS from induction 9,10
Overall survival from induction
1.0
Survival probability ()
0.9
0.8
0.7
0.6
16.9
14.0
0.5
0.4
0.3
0.2
0.1
0
6
18
24
0
12
30
36
Time from randomisation (months)
BSCBest Supportive Care
14
PARAMOUNT PFS and OS results 9,10
PFS HR 0.62 plt0.0001 95 CI 0.49 0.79
15
Based on the results of PARAMOUNT, can response
to induction determine who should receive
maintenance therapy?
16
Progression-free survival HRs in subgroups9,11
17
Pemetrexed continuation maintenance helps improve
survival for patients achieving either SD or a
tumour response following pemetrexed-based
induction10
18
Did study patients get 2nd-line treatments? Were
there any difference between the two
study arms?
19
PARAMOUNT post-discontinuation therapy
(PDT-eligible patients)10
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Are the PARAMOUNT results meaningful from a
patient perspective?
21
What matters to patients
longer survival time
potential additional toxicity
22
Pemetrexed/cisplatin followed by pemetrexed
demonstrated a statistically significant OS
benefit in advanced non-squamous NSCLC10
Overall survival from randomisation
1.0
Induction 4 cycles of
pemetrexed/cisplatin NOT reflected in the data
endpoints
Survival probabality ()
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
6
18
24
0
12
30
36
Time from randomisation (months)
BSCBest Supportive Care
23
2-year survival rate10
placebo BSC 21
pemetrexed BSC 32
21
32
24
PARAMOUNT possible drug related CTCAEs,10
25
PARAMOUNT EQ-5D results9

• EQ-5D results suggest that patients can tolerate
  long-term maintenance treatmentwith pemetrexed
  while maintaining their QoL

26
What matters to patients
PARAMOUNT demonstrated that pemetrexed
continuation maintenance has a positive
risk/benefit ratio can meet all the
requirements for an acceptable continuation
maintenance therapy
longer survival time
potential additional toxicity
27
How do the results of the pemetrexed/cisplatin
induction regimen of PARAMOUNT compare with
those of the pemetrexed/cisplatin-treated
non-squamous patients in study JMDB?
28
PARAMOUNT induction vs JMDB8
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How is PARAMOUNT different from study JMEN?
30
How is PARAMOUNT different from Study JMEN?9,12
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Can we compare pemetrexed continuation versus
pemetrexed switch maintenance therapies?
32
PARAMOUNT9 vs JMEN12
Select the most suitable treatment upfront based
on histology, along with other tumour and
patient characteristics
33
References

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8. Scagliotti GV, et al. Poster presented at 14th
   World Conference on Lung Cancer July 3-7, 2011
   Amsterdam, The Netherlands.
9. Paz-Ares L et al. Maintenance therapy with
   pemetrexed plus best supportive care versus
   placebo plus best supportive care after induction
   therapy with pemetrexed plus cisplatin for
   advanced non-squamous non-small-cell lung cancer
   (PARAMOUNT) a double-blind, phase 3, randomised
   controlled trial. Lancet Oncol 2012 13247-255
10. Paz-Ares L. Presentation at American Society of
    Clinical Oncology Annual Meeting June 1-5, 2012
    Chicago, USA
11. ALIMTA Summary of Product Characteristics. Eli
    Lilly and Company Limited. December 2011.
12. Ciuleanu T et al. Maintenance pemetrexed plus
    best supportive care versus placebo plus best
    supportive care for non-small-cell lung cancer a
    randomized, double-blind, phase 3 study. Lancet
    20093471432-40.