Prsentation PowerPoint

1
The position of neoadjuvant chemotherapy
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Standard of Care
4.2 at 5 years for platinum-based adjuvant Cx
Pignon, ASCO 2006 (7008)
Thoracic Oncology Marseille - France
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Can we improve on the standard?

• Treatment delivery easier to administrate?
• Increase R0 resection rate
• Decrease in distant relapses early treatment of
  micrometastatic disease?
• Decrease in postoperative complications and
  disability sparing lung resection?

Thoracic Oncology Marseille - France
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Reported randomized studies
P, Cisplatin C, Cyclophosphamide V, Vindesine
E, Etoposide M, Mitomycine I, Ifosfamide Cb,
Carboplatine P, Paclitaxel G, Gemcitabine
Thoracic Oncology Marseille - France
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Reported randomized studies
P, Cisplatin C, Cyclophosphamide V, Vindesine
E, Etoposide M, Mitomycine I, Ifosfamide Cb,
Carboplatine T, Paclitaxel G, Gemcitabine
Thoracic Oncology Marseille - France
6
Can we improve on the standard?

• Treatment delivery easier to administrate?
• Increase R0 resection rate
• Decrease in distant relapses early treatment of
  micrometastatic disease?
• Decrease in postoperative complications and
  disability sparing lung resection?

Thoracic Oncology Marseille - France
7
Treatment delivery adjuvant
Kassam, J Thorac Oncol 2007
Thoracic Oncology Marseille - France
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Treatment delivery adjuvant
Full dose of Cx with the pre-planned number of
cycles
Thoracic Oncology Marseille - France
9
Treatment delivery neoadjuvant
NA
2 cycles only
Thoracic Oncology Marseille - France
10
Can we improve on the standard?

• Treatment delivery easier to administrate?
• Increase R0 resection rate
• Decrease in distant relapses early treatment of
  micrometastatic disease?
• Decrease in postoperative complications and
  disability sparing lung resection?

Thoracic Oncology Marseille - France
11
R0 resection rate

• The goal of oncological surgery
• Open and close thoracotomy lt5
• Major impact on survival

i.e. R0
i.e. R1 or R2
i.e. no MLD
Rami-Porta, Eur J Cardio-Thorac Surg 2006
Thoracic Oncology Marseille - France
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Pts with R0 resection rate
NA
2 cycles only
Thoracic Oncology Marseille - France
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PRG on neoadjuvant Cx
NA
NA
2 cycles only
Thoracic Oncology Marseille - France
14
Post-Cx ineligibility for surgery
NA
NA
2 cycles only
Thoracic Oncology Marseille - France
15
Can we improve on the standard?

• Treatment delivery easier to administrate?
• Increase R0 resection rate
• Decrease in distant relapses early treatment of
  micrometastatic disease?
• Decrease in postoperative complications and
  disability sparing lung resection?

Thoracic Oncology Marseille - France
16
Decrease in distant metastasis
P.01
Non Available
2 cycles only
Thoracic Oncology Marseille - France
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Decrease in distant metastasis
Non Available
Thoracic Oncology Marseille - France
18
Can we improve on the standard?

• Treatment delivery easier to administrate?
• Increase R0 resection rate
• Decrease in distant relapses early treatment of
  micrometastatic disease?
• Decrease in postoperative complications and
  disability sparing lung resection?

Thoracic Oncology Marseille - France
19
Sparing lung resection

• Postoperative mortality

Birkmeyer, NEJM 2002
Thoracic Oncology Marseille - France
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Sparing lung resection
Thoracic Oncology Marseille - France
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Sparing lung resection

• Surgical design

How was surgery designed in all the other trials?
Thoracic Oncology Marseille - France
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Sparing lung resection
Thoracic Oncology Marseille - France
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Sparing lung resection

• Is there a price to pay for neoadjuvant Cx?

Mansour, Eur J Cardio-Thorac Surg 2007
Thoracic Oncology Marseille - France
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Can we improve on the standard?

• Treatment delivery YES
• Increase R0 resection rate ?
• Decrease in distant relapses Maybe
• Decrease in lung resection NO

What is the impact of neoadjuvant Cx?
Thoracic Oncology Marseille - France
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Impact on survival
Het ?²(6)1.14, p0.98
6 survival benefit at five years (3-7)
Burdett, J Thorac Oncol 2006
Thoracic Oncology Marseille - France
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Better than adjuvant Cx?

• Neoadjuvant Cx
• HR0.82 (95 CI 0.69-0.97), p.02
• Adjuvant Cx
• HR0.89 (95 CI 0.82-0.96), p.004

Burdett, J Thorac Oncol 2006 Pignon, ASCO 2006
(7008)
Thoracic Oncology Marseille - France
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Front Door vs. Back Door hypothesis

• Pre-op trials

100 Cx

• Post-op trials

80 Cx
E Vallières
Thoracic Oncology Marseille - France
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Perspectives

• Awaiting final results of closed trials
• ChEST CDDP/GEM surgery vs surgery alone
• LU22 Cis-combo x 3 surgery vs surgery alone
• IFCT 0002 Platinum-based Cx x 2 vs 4 plus surgery

Thoracic Oncology Marseille - France
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Perspectives

• Compare to adjuvant Cx
• NATCH trial (completed - ASCO 2007?)
• PhIIR EORTC (CDDP/MTA)
• PhIII China (CBDCA/TXT)

Thoracic Oncology Marseille - France
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Perspectives

• Improve activity neoadjuvant Cx?
• Cx Drugs?
• Number of cycles? (IFCT0002)
• New drugs? Alone? Combination?
• Combination with Rx?

Thoracic Oncology Marseille - France
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Perspectives

• Improve surgical selection?
• Avoid (right) pneumonectomy? (especially for
  pT0N0!)
• Promote alternative surgical techniques
• New preoperative tools (18FDG-TEP?)

Thoracic Oncology Marseille - France
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Perspectives

• Tailoring perioperative Cx?
• Adjuvant Cx
• IHC ERCC1
• Gene profile
• Neoadjuvant Cx?
• qRT-PCR RRM1

Olaussen, NEJM 2006 Potti, NEJM 2006 Rosell, Clin
Cancer Res 2004
Thoracic Oncology Marseille - France
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Conclusions

• Neoadjuvant Cx in early stages NSCLC
• Is easily feasible
• Improves survival over surgery alone
• Opens new questions regarding surgical management
• Remains experimental until the results of phase
  III randomized studies vs adjuvant Cx

Thoracic Oncology Marseille - France