有效的非小细胞肺癌治疗的基础-Nicholas Thatcher-2009CSCO年会
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有效的非小细胞肺癌治疗的基础-Nicholas Thatcher-2009CSCO年会
AVASTIN FIRST LINE IN ADVANCED NON SQUAMOUS NSCLC
Nick Thatcher, Christie Hospital, Manchester, England
ANTI-VEGF THERAPY: MECHANISM OF ACTION
– No evidence of tumour invading or abutting major blood vessels; no spinal cord compression; ulceration, bone fractures or wound-healing complications
Mancuso et al. J Clin Invest 2006 (Ellis and Haller J Clin Oncol 2008)
PIVOTAL STUDIES OF AVASTIN IN COMBINATION WITH PLATINUM-CONTAINING CHEMOTHERAPY
PD PD* PD
PHASE III TRIALS OF AVASTIN (E4599 VS. AVAIL): ELIGIBILITY CRITERIA AND SAFETY
• E45991 and AVAiL2 evaluated Avastin in combination with CP and CG,
EFFECTS OF VEGF INHIBITION: inhibition of recurrent vessel growth
• Revascularisation following discontinuation of antiVEGF therapy
Untreated
Anti-VEGF, 7 days Withdrawal, 2 days Withdrawal, 7 days
CP (n=444)
PD*
Avastin 15mg/kg† Avastin
+ CP (n=434)
PD
AVAiL (Ex-US) Reck et al J Clin Oncol 2009
Previously untreated, stage IIIB, IV or recurrent non-squamous NSCLC (n=1,043)
E4599 (US) Sandler et al
N Engl J Med 2006
Previously untreated stage IIIB/IV
non-squamous NSCLC (n=878)
•no gross hemoptysis •no therapeutic anticoagulation •no brain metastases
•As above •no evidence of tumour invading or abutting major blood vessels •no spinal cord compression, ulceration, bone fractures or wound-healing complications
respectively
• Inclusion/exclusion criteria were comparable, with additional considerations in AVAiL
– ECOG PS 0-1 ; Non-squamous cell no haemoptysis, <1/2 tsp bright red blood ;CNS metastases; thrombotic ,bleeding disorders; anticoagulants ,aspirin, NSAIDs; significant cardiovascular disease
AvAavsatsintin 7.5mg/kg† + CG
(n=345)
Placebo + CG (n=347)
AvAavsatsintin 15mg/kg† + CG
(n=3Байду номын сангаас1)
*No cross over permitted; †Dose of Avastin every 3 weeks CG = cisplatin/gemcitabine; CP = carboplatin/paclitaxel; PD = progressive disease
EARLY EFFECTS
CONTINUED EFFECTS
Regression of existing tumour microvasculature1-7
Normalisation of remaining tumour vasculature5-8
Inhibition of new tumour vasculature1,2,9,10
References: 1. Baluk P et al. Curr Opin Genet Dev. 2005;15:102-111. 2. Inai T et al. Am J Pathol. 2004;165:35-52. 3. Erber R et al. FASEB J. 2004;18:338-340. 4. Tong RT et al. Cancer Res. 2004;64:3731-3736. 5. Jain RK. Nat Med. 2001;7:987-989. 6. Jain RK. Science. 2005;307:58-62. 7. Lee CG et al. Cancer Res. 2000;60:5565-5570. 8. Willett CG et al. Nat Med. 2004;10:145-147. 9. Gerber HP et al. Cancer Res. 2005;65:671-680. 10. Warren RS et al. J Clin Invest. 1995;95:1789-1797.
AVASTIN FIRST LINE IN ADVANCED NON SQUAMOUS NSCLC
Nick Thatcher, Christie Hospital, Manchester, England
ANTI-VEGF THERAPY: MECHANISM OF ACTION
– No evidence of tumour invading or abutting major blood vessels; no spinal cord compression; ulceration, bone fractures or wound-healing complications
Mancuso et al. J Clin Invest 2006 (Ellis and Haller J Clin Oncol 2008)
PIVOTAL STUDIES OF AVASTIN IN COMBINATION WITH PLATINUM-CONTAINING CHEMOTHERAPY
PD PD* PD
PHASE III TRIALS OF AVASTIN (E4599 VS. AVAIL): ELIGIBILITY CRITERIA AND SAFETY
• E45991 and AVAiL2 evaluated Avastin in combination with CP and CG,
EFFECTS OF VEGF INHIBITION: inhibition of recurrent vessel growth
• Revascularisation following discontinuation of antiVEGF therapy
Untreated
Anti-VEGF, 7 days Withdrawal, 2 days Withdrawal, 7 days
CP (n=444)
PD*
Avastin 15mg/kg† Avastin
+ CP (n=434)
PD
AVAiL (Ex-US) Reck et al J Clin Oncol 2009
Previously untreated, stage IIIB, IV or recurrent non-squamous NSCLC (n=1,043)
E4599 (US) Sandler et al
N Engl J Med 2006
Previously untreated stage IIIB/IV
non-squamous NSCLC (n=878)
•no gross hemoptysis •no therapeutic anticoagulation •no brain metastases
•As above •no evidence of tumour invading or abutting major blood vessels •no spinal cord compression, ulceration, bone fractures or wound-healing complications
respectively
• Inclusion/exclusion criteria were comparable, with additional considerations in AVAiL
– ECOG PS 0-1 ; Non-squamous cell no haemoptysis, <1/2 tsp bright red blood ;CNS metastases; thrombotic ,bleeding disorders; anticoagulants ,aspirin, NSAIDs; significant cardiovascular disease
AvAavsatsintin 7.5mg/kg† + CG
(n=345)
Placebo + CG (n=347)
AvAavsatsintin 15mg/kg† + CG
(n=3Байду номын сангаас1)
*No cross over permitted; †Dose of Avastin every 3 weeks CG = cisplatin/gemcitabine; CP = carboplatin/paclitaxel; PD = progressive disease
EARLY EFFECTS
CONTINUED EFFECTS
Regression of existing tumour microvasculature1-7
Normalisation of remaining tumour vasculature5-8
Inhibition of new tumour vasculature1,2,9,10
References: 1. Baluk P et al. Curr Opin Genet Dev. 2005;15:102-111. 2. Inai T et al. Am J Pathol. 2004;165:35-52. 3. Erber R et al. FASEB J. 2004;18:338-340. 4. Tong RT et al. Cancer Res. 2004;64:3731-3736. 5. Jain RK. Nat Med. 2001;7:987-989. 6. Jain RK. Science. 2005;307:58-62. 7. Lee CG et al. Cancer Res. 2000;60:5565-5570. 8. Willett CG et al. Nat Med. 2004;10:145-147. 9. Gerber HP et al. Cancer Res. 2005;65:671-680. 10. Warren RS et al. J Clin Invest. 1995;95:1789-1797.