Transcript Research To Practice

PARAMOUNT: Phase III Study of
Maintenance Pemetrexed (Pem) plus
Best Supportive Care (BSC) versus
Placebo plus BSC Immediately
Following Induction Treatment with
Pem plus Cisplatin for Advanced
Nonsquamous Non-Small Cell Lung
Cancer
Paz-Ares LG et al.
Proc ASCO 2011;Abstract CRA7510.
Maintenance Therapy:
Continuation vs Switch
• Continuation maintenance
– Continual suppression of malignancy will be
more effective than intermittent use
• Switch maintenance (planned sequential)
– Transition to proven second-line therapy before
the emergence of resistance
– Early use assures exposure to second-line
therapy (ie, “no one falls off the cliff”)
Edelman MJ. Proc ASCO 2011;Discussant.
PARAMOUNT Phase III Study of
Pemetrexed Continuation Maintenance
Patient Eligibility:
• Nonsquamous NSCLC
• No prior systemic therapy
Continuation
Maintenance (until PD)
Induction
Pem + BSC
Pem + cisplatin d1,
d1, q21days
q21days x 4
CR, PR
SD
R
2:1
Continuation
Maintenance (until PD)
Placebo + BSC
d1, q21days
Paz-Ares LG et al. Proc ASCO 2011;Abstract CRA7510.
Progression-Free Survival (PFS)
from Maintenance: Independent Review
Median PFS*
(months)
Pem + BSC
(n = 316)
Placebo + BSC
(n = 156)
3.9
2.6
Hazard ratio: 0.64, p = 0.0002
* 88% of patients were independently reviewed (472/539).
Paz-Ares LG et al. Proc ASCO 2011;Abstract CRA7510.
Tumor Response* from Maintenance
Independent Review
Pemetrexed
(n = 316)
Placebo
(n = 156)
p-value
9 (2.8%)
1 (0.6%)
0.176
0
0
9 (2.8%)
1 (0.6%)
Stable disease
218 (69.0%)
92 (59.0%)
—
Disease control rate
227 (71.8%)
93 (59.6%)
0.009
Response rate
Complete response
Partial response
*Response represents a further tumor reduction from the baseline response to
induction therapy.
Paz-Ares LG et al. Proc ASCO 2011;Abstract CRA7510.
Select Grade 3 and 4
Drug-Related Toxicities
Pemetrexed
(n = 359)
Placebo
(n = 180)
Fatigue*
4.2%
0.6%
Anemia*
4.5%
0.6%
Neutropenia*
3.6%
0
Leukopenia
1.7%
0
Sensory neuropathy
0.3%
0.6%
Mucositis/stomatitis
0.3%
0
ALT (SGPT)
0.3%
0
Adverse event
* Statistically significant between arms (p ≤ 0.05)
Paz-Ares LG et al. Proc ASCO 2011;Abstract CRA7510.
Conclusions
• The trial met its primary PFS endpoint as
pemetrexed maintenance therapy resulted in a
significant benefit compared to placebo for patients
with advanced nonsquamous NSCLC (3.9 mo vs
2.6 mo; HR = 0.64).
• Pemetrexed maintenance was well tolerated.
• Mature OS data are pending.
Paz-Ares LG et al. Proc ASCO 2011;Abstract CRA7510.
Investigator Commentary: Continuation Maintenance with
Pemetrexed for Advanced Nonsquamous NSCLC
The main question of the PARAMOUNT trial was how effective would
continuation maintenance be with pemetrexed. The progression-free
survival results were consistent with their previous reports. Although
they remained statistically significant, they were not as dramatic. I
believe these results can be used by community oncologists as validation
that you can start with a pemetrexed-based doublet with platinum up
front and then continue the pemetrexed as maintenance. Some will
argue that continuation maintenance is not as effective as switch
maintenance, and this is a topic that will remain debatable in the future.
The important message from PARAMOUNT is that pemetrexed
maintenance is safe to administer and the PFS benefit is maintained. It
is an acceptable standard in addition to other regimens that clinicians
use to treat patients. I personally was not a big believer in maintenance
therapy, but I do use it now. Continuing to treat a patient with a
therapeutic agent seems to help.
Edward S Kim, MD