The Very Best, Most Perfect Possible Way to Treat Advanced Colorectal Cancer in 2005: Agent Choice and Ideal Sequencing Charles D. Blanke, M.D. OHSU Cancer Institute
FIRE Trial: Abstract #3516 Comparison of infusional 5FU + irinotecan (AI2-IRI) versus irinotecan + oxaliplatin (IROX) Primary end-point: Progression-free survival Secondary end-points: ORR, OS, liver met resectability, toxicity A. Schalhorn et al.
FIRE Trial: Abstract #3516 Comparison of infusional 5FU + irinotecan (AI2-IRI) versus irinotecan + oxaliplatin (IROX) Primary end-point: Progression-free survival Secondary end-points: ORR, OS, liver met resectability, toxicity
FIRE Trial: Abstract #3516 Comparison of infusional 5FU + irinotecan (AI2-IRI) versus irinotecan + oxaliplatin (IROX) Primary end-point: Progression-free survival Secondary end-points: ORR, OS, liver met resectability, toxicity
FIRE Results and Conclusions Infus 5FU-I IROXp Objective responses (%)4548NS PFS (months) Overall survival day mortality (%) Authors: Regimens are comparable in regard to ORR, PFS, OS, and toxicity
FIRE Results and Conclusions Infus 5FU-I IROXp Objective responses (%)4548NS PFS (months) Overall survival day mortality (%) Authors: Regimens are comparable in regard to ORR, PFS, OS, and toxicity
FIRE Results and Conclusions Infus 5FU-I IROXp Objective responses (%)4548NS PFS (months) Overall survival day mortality (%) Authors: Regimens are comparable in regard to ORR, PFS, OS, and toxicity
FIRE Results and Conclusions Infus 5FU-I IROXp Objective responses (%)4548NS PFS (months) Overall survival day mortality (%) Authors: Regimens are comparable in regard to ORR, PFS, OS, and toxicity
FIRE Results and Conclusions Infus 5FU-I IROXp Objective responses (%)4548NS PFS (months) Overall survival day mortality (%) Authors: Regimens are comparable in regard to ORR, PFS, OS, and toxicity
FIRE: Commentary Infusional 5FU-irinotecan and IROX results for both arms are similar to those from previous phase III studies IROX was previously shown to offer similar PFS and improved overall survival vs. bolus IFL There may be a hint that IROX is not quite as good as regimens (irinotecan or oxaliplatin-based) that include infusional 5FU IROX would not be my first choice –IROX remains a perfectly reasonable regimen in select patients
FIRE: Commentary Infusional 5FU-irinotecan and IROX results for both arms are similar to those from previous phase III studies IROX was previously shown to offer similar PFS and improved overall survival vs. bolus IFL There may be a hint that IROX is not quite as good as regimens (irinotecan or oxaliplatin-based) that include infusional 5FU IROX would not be my first choice –IROX remains a perfectly reasonable regimen in select patients
FIRE: Commentary Infusional 5FU-irinotecan and IROX results for both arms are similar to those from previous phase III studies IROX was previously shown to offer similar PFS and improved overall survival vs. bolus IFL There may be a hint that IROX is not quite as good as regimens (irinotecan or oxaliplatin-based) that include infusional 5FU IROX would not be my first choice –IROX remains a perfectly reasonable regimen in select patients
FIRE: Commentary Infusional 5FU-irinotecan and IROX results for both arms are similar to those from previous phase III studies IROX was previously shown to offer similar PFS and improved overall survival vs. bolus IFL There may be a hint that IROX is not quite as good as regimens (irinotecan or oxaliplatin-based) that include infusional 5FU IROX would not be my first choice –IROX remains a perfectly reasonable regimen in select patients
FIRE: Commentary Infusional 5FU-irinotecan and IROX results for both arms are similar to those from previous phase III studies IROX was previously shown to offer similar PFS and improved overall survival vs. bolus IFL There may be a hint that IROX is not quite as good as regimens (irinotecan or oxaliplatin-based) that include infusional 5FU IROX would not be my first choice –IROX remains a perfectly reasonable regimen in select patients
FIRE: Commentary Infusional 5FU-irinotecan and IROX results for both arms are similar to those from previous phase III studies IROX was previously shown to offer similar PFS and improved overall survival vs. bolus IFL There may be a hint that IROX is not quite as good as regimens (irinotecan or oxaliplatin-based) that include infusional 5FU IROX would not be my first choice –IROX remains a perfectly reasonable regimen in select patients
LIFE Trial: Abstract #3517 5FU monotherapy (Lokich or de Gramont) 5FU + oxaliplatin RANDOMIZATIONRANDOMIZATION Primary endpoint : 10% increase 2-year survival (20 to 30%) Note: FOLFOX4 2-year survival on N9741 was ~40% 725 pts IrinotecanIrinotecan PROGRESSIONPROGRESSION A. Pluzanska et al.
LIFE Trial: Abstract #3517 5FU monotherapy (Lokich or de Gramont) 5FU + oxaliplatin RANDOMIZATIONRANDOMIZATION Primary endpoint : 10% increase 2-year survival (20 to 30%) Note: FOLFOX4 2-year survival on N9741 was ~40% 725 pts IrinotecanIrinotecan PROGRESSIONPROGRESSION
LIFE Trial: Abstract #3517 5FU monotherapy (Lokich or de Gramont) 5FU + oxaliplatin RANDOMIZATIONRANDOMIZATION Primary endpoint : 10% increase 2-year survival (20 to 30%) Note: FOLFOX4 2-year survival on N9741 was ~40% 725 pts IrinotecanIrinotecan PROGRESSIONPROGRESSION
LIFE Trial: Abstract #3517 5FU monotherapy (Lokich or de Gramont) 5FU + oxaliplatin RANDOMIZATIONRANDOMIZATION Primary endpoint : 10% increase 2-year survival (20 to 30%) Note: FOLFOX4 2-year survival on N9741 was ~40% 725 pts IrinotecanIrinotecan PROGRESSIONPROGRESSION
LIFE Results and Conclusions* Oxaliplatin5FU alonep Objective response rate (%)5430< PFS (months)7.95.9< year survival (%)2523NS ORR and PFS are improved with combination therapy Survival results are explained by the low percentage getting irinotecan *
LIFE Results and Conclusions* Oxaliplatin5FU alonep Objective response rate (%)5430< PFS (months)7.95.9< year survival (%)2523NS ORR and PFS are improved with combination therapy Survival results are explained by the low percentage getting irinotecan *
LIFE Results and Conclusions* Oxaliplatin5FU alonep Objective response rate (%)5430< PFS (months)7.95.9< year survival (%)2523NS ORR and PFS are improved with combination therapy Survival results are explained by the low percentage getting irinotecan *
LIFE Results and Conclusions* Oxaliplatin5FU alonep Objective response rate (%)5430< PFS (months)7.95.9< year survival (%)2523NS ORR and PFS are improved with combination therapy Survival results are explained by the low percentage getting irinotecan *
FOCUS: Abstract #3518 Upfront Strategies for Chemotherapy Drug A until it fails… then B until it fails “staged single agents” A Drug A until it fails… then add drug B until both fail “staged combination” B Drugs A + B together until both fail “1 st -line combination” C M.T. Seymour, et al.
FOCUS: Abstract #3518 Upfront Strategies for Chemotherapy Drug A until it fails… then B until it fails “staged single agents” A Drug A until it fails… then add drug B until both fail “staged combination” B Drugs A + B together until both fail “1 st -line combination” C
FOCUS: Abstract #3518 Upfront Strategies for Chemotherapy Drug A until it fails… then B until it fails “staged single agents” A Drug A until it fails… then add drug B until both fail “staged combination” B Drugs A + B together until both fail “1 st -line combination” C
FOCUS: Abstract #3518 Upfront Strategies for Chemotherapy Drug A until it fails… then B until it fails “staged single agents” A Drug A until it fails… then add drug B until both fail “staged combination” B Drugs A + B together until both fail “1 st -line combination” C
A: FU until it fails, then change to Ir B(ir): FU until it fails, then add Ir B(ox): FU until it fails, then add Ox C(ir): FU+Ir from the start, until it fails C(ox): FU+Ox from the start, until it fails 1/3 1/ patients FOCUS Primary endpoint: Overall Survival
A: FU until it fails, then change to Ir B(ir): FU until it fails, then add Ir B(ox): FU until it fails, then add Ox C(ir): FU+Ir from the start, until it fails C(ox): FU+Ox from the start, until it fails 1/3 1/ patients FOCUS Primary endpoint: Overall Survival
A: FU until it fails, then change to Ir B(ir): FU until it fails, then add Ir B(ox): FU until it fails, then add Ox C(ir): FU+Ir from the start, until it fails C(ox): FU+Ox from the start, until it fails 1/3 1/ patients FOCUS Primary endpoint: Overall Survival
A: FU until it fails, then change to Ir B(ir): FU until it fails, then add Ir B(ox): FU until it fails, then add Ox C(ir): FU+Ir from the start, until it fails C(ox): FU+Ox from the start, until it fails 1/3 1/ patients FOCUS Primary endpoint: Overall Survival
A: FU until it fails, then change to Ir 3 rd drug salvage B(ir): FU until it fails, then add Ir B(ox): FU until it fails, then add Ox C(ir): FU+Ir from the start, until it fails C(ox): FU+Ox from the start, until it fails 1/3 1/ patients FOCUS Primary endpoint: Overall Survival OxCap IrCap OxCap IrCap
A: FU until it fails, then change to Ir 3 rd drug salvage B(ir): FU until it fails, then add Ir B(ox): FU until it fails, then add Ox C(ir): FU+Ir from the start, until it fails C(ox): FU+Ox from the start, until it fails 1/3 1/ patients FOCUS Primary endpoint: Overall Survival OxCap IrCap OxCap IrCap
FOCUS Response to 1 st -Line Chemotherapy MdG Plans A & B IrMdG Plan C(ir) OxMdG Plan C(ox) n CR+PR28.9%51.3%57.0% SD47.5%37.8%29.2% PD23.7%10.9%13.8%
FOCUS Response to 1 st -Line Chemotherapy MdG Plans A & B IrMdG Plan C(ir) OxMdG Plan C(ox) n CR+PR28.9%51.3%57.0% SD47.5%37.8%29.2% PD23.7%10.9%13.8%
FOCUS Response to 1 st -Line Chemotherapy MdG Plans A & B IrMdG Plan C(ir) OxMdG Plan C(ox) n CR+PR 28.9% 51.3%57.0% SD47.5%37.8%29.2% PD23.7%10.9%13.8%
Proportion Months Plan regimen median PFS A MdG 6.3 mo B(ir) MdG 6.7 mo B(ox) MdG 6.4 mo C(ir) IrMdG 8.6 mo C(ox) OxMdG 8.8 mo Progression-Free Survival, 1st Line
Plan A Plan B(ir) Plan C(ir) Plan B(ox) Plan C(ox) S u r v i v a l Months Overall Survival by Individual Treatment Arm
FOCUS Author Conclusions: Confirms higher RR, PFS and toxicity of combination chemotherapy However, deferring the combination until after optimum FU alone gave equal overall survival with less early toxicity
FOCUS Author Conclusions: Confirms higher RR, PFS and toxicity of combination chemotherapy However, deferring the combination until after optimum FU alone gave equal overall survival with less early toxicity
Problems in LIFE/FOCUS Interpretation Median survival low throughout all arms of both studies Why did irinotecan added to 5FU after 5FU failure, work better than replacing 5FU with irinotecan? How do we integrate biologic therapy into the sequencing question?
Problems in LIFE/FOCUS Interpretation Median survival low throughout all arms of both studies Why did irinotecan added to 5FU after 5FU failure, work better than replacing 5FU with irinotecan? How do we integrate biologic therapy into the sequencing question?
Problems in LIFE/FOCUS Interpretation Median survival low throughout all arms of both studies Why did irinotecan added to 5FU after 5FU failure, work better than replacing 5FU with irinotecan? How do we integrate biologic therapy into the sequencing question?
Problems in LIFE/FOCUS Interpretation Median survival low throughout all arms of both studies Why did irinotecan added to 5FU after 5FU failure, work better than replacing 5FU with irinotecan? How do we integrate biologic therapy into the sequencing question?
Additional LIFE/FOCUS Commentary There are patients who should receive combination therapy up- front –Potentially resectable for cure –Highly symptomatic patients –?Poor PS patients, related to cancer –Asymptomatic intact primary, not going to surgery –Carcinomatosis This provides additional impetus for using FOLFIRI (or CapIRI) after FOLFOX failure, instead of irinotecan alone FOLFOX = FOLFIRI
Additional LIFE/FOCUS Commentary There are patients who should receive combination therapy up- front –Potentially resectable for cure –Highly symptomatic patients –?Poor PS patients, related to cancer –Asymptomatic intact primary, not going to surgery –Carcinomatosis This provides additional impetus for using FOLFIRI (or CapIRI) after FOLFOX failure, instead of irinotecan alone FOLFOX = FOLFIRI
Additional LIFE/FOCUS Commentary There are patients who should receive combination therapy up- front –Potentially resectable for cure –Highly symptomatic patients –?Poor PS patients, related to cancer –Asymptomatic intact primary, not going to surgery –Carcinomatosis This provides additional impetus for using FOLFIRI (or CapIRI) after FOLFOX failure, instead of irinotecan alone FOLFOX = FOLFIRI
Additional LIFE/FOCUS Commentary There are patients who should receive combination therapy up- front –Potentially resectable for cure –Highly symptomatic patients –?Poor PS patients, related to cancer –Asymptomatic intact primary, not going to surgery –Carcinomatosis This provides additional impetus for using FOLFIRI (or CapIRI) after FOLFOX failure, instead of irinotecan alone FOLFOX = FOLFIRI
Additional LIFE/FOCUS Commentary There are patients who should receive combination therapy up- front –Potentially resectable for cure –Highly symptomatic patients –?Poor PS patients, related to cancer –Asymptomatic intact primary, not going to surgery –Carcinomatosis This provides additional impetus for using FOLFIRI (or CapIRI) after FOLFOX failure, instead of irinotecan alone FOLFOX = FOLFIRI
Additional LIFE/FOCUS Commentary There are patients who should receive combination therapy up- front –Potentially resectable for cure –Highly symptomatic patients –?Poor PS patients, related to cancer –Asymptomatic intact primary, not going to surgery –Carcinomatosis This provides additional impetus for using FOLFIRI (or CapIRI) after FOLFOX failure, instead of irinotecan alone FOLFOX = FOLFIRI
N9841: Results of Third-Line Therapy (Abstract #3519) N9841: Randomized phase III trial of second-line FOLFOX4 versus CPT-11 in 5FU failures Patients failing second-line were crossed over to the “opposite” regimen This is a report of third-line results: Protocol-mandated but not randomized EndpointCPT-11FOLFOX4p ORR (%)1527<0.01 Median TTP (mo) K.M. Rowland, et al.
N9841: Results of Third-Line Therapy (Abstract #3519) N9841: Randomized phase III trial of second-line FOLFOX4 versus CPT-11 in 5FU failures Patients failing second-line were crossed over to the “opposite” regimen This is a report of third-line results: Protocol-mandated but not randomized EndpointCPT-11FOLFOX4p ORR (%)1527<0.01 Median TTP (mo)
N9841: Results of Third-Line Therapy (Abstract #3519) N9841: Randomized phase III trial of second-line FOLFOX4 versus CPT-11 in 5FU failures Patients failing second-line were crossed over to the “opposite” regimen This is a report of third-line results: Protocol-mandated but not randomized EndpointCPT-11FOLFOX4p ORR (%)1527<0.01 Median TTP (mo)
N9841: Results of Third-Line Therapy (Abstract #3519) N9841: Randomized phase III trial of second-line FOLFOX4 versus CPT-11 in 5FU failures Patients failing second-line were crossed over to the “opposite” regimen This is a report of third-line results: Protocol-mandated but not randomized EndpointCPT-11FOLFOX4p ORR (%)1527<0.01 Median TTP (mo)
N9841: Results of Third-Line Therapy (Abstract #3519) N9841: Randomized phase III trial of second-line FOLFOX4 versus CPT-11 in 5FU failures Patients failing second-line were crossed over to the “opposite” regimen This is a report of third-line results: Protocol-mandated but not randomized EndpointCPT-11FOLFOX4p ORR (%)1527<0.01 Median TTP (mo)
N9841 Results and Conclusion(s)* CPT-11 FOLFOX N = 126 FOLFOX CPT-11 N = 94 ORR (%)164 Median TTP (mo)52.7 Median Survival (mo) Severe Diarrhea (%)1728 Paresthesias (%)124 Both regimens are active third-line*
N9841 Results and Conclusion(s)* CPT-11 FOLFOX N = 126 FOLFOX CPT-11 N = 94 ORR (%)164 Median TTP (mo)52.7 Median Survival (mo) Severe Diarrhea (%)1728 Paresthesias (%)124 Both regimens are active third-line*
N9841 Results and Conclusion(s)* CPT-11 FOLFOX N = 126 FOLFOX CPT-11 N = 94 ORR (%)164 Median TTP (mo)52.7 Median Survival (mo) Severe Diarrhea (%)1728 Paresthesias (%)124 Both regimens are active third-line*
N9841 Results and Conclusion(s)* CPT-11 FOLFOX N = 126 FOLFOX CPT-11 N = 94 ORR (%)164 Median TTP (mo)52.7 Median Survival (mo) Severe Diarrhea (%)1728 Paresthesias (%)124 Both regimens are active third-line*
N9841 Results and Conclusion(s)* CPT-11 FOLFOX N = 126 FOLFOX CPT-11 N = 94 ORR (%)164 Median TTP (mo)52.7 Median Survival (mo) Severe Diarrhea (%)1728 Paresthesias (%)124 Both regimens are active third-line*
N9841: Commentary Results look remarkably like 2 nd -line crossover results from Tournigand: –FOLFOX 15% ORR; 4.2 month PFS –FOLFIRI 4% ORR; 2.5 month PFS No shockers in toxicity patterns Only 44% of patients received third-line therapy Back to confusion over FOLFIRI versus irinotecan alone after fluoropyrimidine failure
N9841: Commentary Results look remarkably like 2 nd -line crossover results from Tournigand: –FOLFOX 15% ORR; 4.2 month PFS –FOLFIRI 4% ORR; 2.5 month PFS No shockers in toxicity patterns Only 44% of patients received third-line therapy Back to confusion over FOLFIRI versus irinotecan alone after fluoropyrimidine failure
N9841: Commentary Results look remarkably like 2 nd -line crossover results from Tournigand: –FOLFOX 15% ORR; 4.2 month PFS –FOLFIRI 4% ORR; 2.5 month PFS No shockers in toxicity patterns Only 44% of patients received third-line therapy Back to confusion over FOLFIRI versus irinotecan alone after fluoropyrimidine failure
N9841: Commentary Results look remarkably like 2 nd -line crossover results from Tournigand: –FOLFOX 15% ORR; 4.2 month PFS –FOLFIRI 4% ORR; 2.5 month PFS No shockers in toxicity patterns Only 44% of patients received third-line therapy Back to confusion over FOLFIRI versus irinotecan alone after fluoropyrimidine failure
N9841: Commentary Results look remarkably like 2 nd -line crossover results from Tournigand: –FOLFOX 15% ORR; 4.2 month PFS –FOLFIRI 4% ORR; 2.5 month PFS No shockers in toxicity patterns Only 44% of patients received third-line therapy Back to confusion over FOLFIRI versus irinotecan alone after fluoropyrimidine failure
mFOLFOX6mFOLFOX6 CapOXCapOX bFOLbFOL RANDOMIZATIONRANDOMIZATION TREE Studies: TREE-1 Abstract #3515 H.S.Hochster, et al.
mFOLFOX6 + bevacizumab 5 mg/kg mFOLFOX6 + bevacizumab 5 mg/kg CapOX + bevacizumab 7.5mg/kg bFOL + bevacizumab 5mg/kg RANDOMIZATIONRANDOMIZATION TREE Studies: TREE-2
mFOLFOX6 + bevacizumab 5 mg/kg mFOLFOX6 + bevacizumab 5 mg/kg CapOX + bevacizumab 7.5mg/kg bFOL + bevacizumab 5mg/kg RANDOMIZATIONRANDOMIZATION TREE Studies: TREE-2 *Doses same TREE except capecitabine 850/m2 BID vs 1000
mFOLFOX6 + bevacizumab 5 mg/kg mFOLFOX6 + bevacizumab 5 mg/kg CapOX + bevacizumab 7.5mg/kg bFOL + bevacizumab 5mg/kg RANDOMIZATIONRANDOMIZATION TREE Studies Primary endpoint was grade 3/4 toxicity Secondary endpoints: ORR, TTP, OS, TTF, comparative safety
mFOLFOX6 + bevacizumab 5 mg/kg mFOLFOX6 + bevacizumab 5 mg/kg CapOX + bevacizumab 7.5mg/kg bFOL + bevacizumab 5mg/kg RANDOMIZATIONRANDOMIZATION TREE Studies Primary endpoint was grade 3/4 toxicity Secondary endpoints: ORR, TTP, OS, TTF, comparative safety
Response Rates: TREE 1 and 2 mFOLFOXbFOLCAPOX WithoutWith bevWithoutWith bevWithoutWith bev ORR (%) (95% CI) 41 (27-56) 52 (39-64) 20 (10-34) 34 (23-75) 27 (15-42) 46 (34-58)
Response Rates: TREE 1 and 2 mFOLFOXbFOLCAPOX WithoutWith bevWithoutWith bevWithoutWith bev ORR (%) (95% CI) 41 (27-56) 52 (39-64) 20 (10-34) 34 (23-75) 27 (15-42) 46 (34-58)
Response Rates: TREE 1 and 2 mFOLFOXbFOLCAPOX WithoutWith bevWithoutWith bevWithoutWith bev ORR (%) (95% CI) 41 (27-56) 52 (39-64) 20 (10-34) 34 (23-75) 27 (15-42) 46 (34-58)
Response Rates: TREE 1 and 2 mFOLFOXbFOLCAPOX WithoutWith bevWithoutWith bevWithoutWith bev ORR (%) (95% CI) 41 (27-56) 52 (39-64) 20 (10-34) 34 (23-75) 27 (15-42) 46 (34-58)
Response Rates: bFOL versus Others mFOLFOXbFOLCAPOX With bev ORR (%) (95% CI) 52 (39-64) 34 (23-75) 46 (34-58)
TREE-1 vs. TREE-2 Comparative Time to Treatment Failure (TTF) Events mFOLFOXmFOLFOX-BbFOLbFOL-BCapOXCapOX-B TTF (mo) % CI( )( )( )( )( )( )
TREE Commentary While TREE 1 and 2 were not a randomized comparison, similarity of patient population allows fairly robust comparison Bevacizumab greatly improved response rates of all 3 regimens –Bolus 5FU with oxaliplatin appears less effective than infusional and CapOX Eagerly await TTP and OS data Bevacizumab improved time-to-treatment failure for bFOL and CapOX, but not FOLFOX
TREE Commentary While TREE 1 and 2 were not a randomized comparison, similarity of patient population allows fairly robust comparison Bevacizumab greatly improved response rates of all 3 regimens –Bolus 5FU with oxaliplatin appears less effective than infusional and CapOX Eagerly await TTP and OS data Bevacizumab improved time-to-treatment failure for bFOL and CapOX, but not FOLFOX
TREE Commentary While TREE 1 and 2 were not a randomized comparison, similarity of patient population allows fairly robust comparison Bevacizumab greatly improved response rates of all 3 regimens –Bolus 5FU with oxaliplatin appears less effective than infusional and CapOX Eagerly await TTP and OS data Bevacizumab improved time-to-treatment failure for bFOL and CapOX, but not FOLFOX
TREE Commentary While TREE 1 and 2 were not a randomized comparison, similarity of patient population allows fairly robust comparison Bevacizumab greatly improved response rates of all 3 regimens –Bolus 5FU with oxaliplatin appears less effective than infusional and CapOX Eagerly await TTP and OS data Bevacizumab improved time-to-treatment failure for bFOL and CapOX, but not FOLFOX
Panitumumab Monotherapy in CRC: Abstract #3520 Background: Panitumumab is a fully humanized monoclonal Ab that inhibits EGFR Phase 2 trial in 148 patients failing standard chemotherapy –Failure of 5FU and CPT-11, oxali, or both Primary endpoint: Objective response –RECIST criteria Divided patients into 2 cohorts: A = High EGFR staining; B = low-level staining I. Malik, et al.
Panitumumab Monotherapy in CRC: Abstract #3520 Background: Panitumumab is a fully humanized monoclonal Ab that inhibits EGFR Phase 2 trial in 148 patients failing standard chemotherapy –Failure of 5FU and CPT-11, oxali, or both Primary endpoint: Objective response –RECIST criteria Divided patients into 2 cohorts: A = High EGFR staining; B = low-level staining
Panitumumab Monotherapy in CRC: Abstract #3520 Background: Panitumumab is a fully humanized monoclonal Ab that inhibits EGFR Phase 2 trial in 148 patients failing standard chemotherapy –Failure of 5FU and CPT-11, oxali, or both Primary endpoint: Objective response –RECIST criteria Divided patients into 2 cohorts: A = High EGFR staining; B = low-level staining
Panitumumab Monotherapy in CRC: Abstract #3520 Background: Panitumumab is a fully humanized monoclonal Ab that inhibits EGFR Phase 2 trial in 148 patients failing standard chemotherapy –Failure of 5FU and CPT-11, oxali, or both Primary endpoint: Objective response –RECIST criteria Divided patients into 2 cohorts: A = High EGFR staining; B = low-level staining
Panitumumab Monotherapy in CRC: Abstract #3520 Background: Panitumumab is a fully humanized monoclonal Ab that inhibits EGFR Phase 2 trial in 148 patients failing standard chemotherapy –Failure of 5FU and CPT-11, oxali, or both Primary endpoint: Objective response –RECIST criteria Divided patients into 2 cohorts: A = High EGFR staining; B = low-level staining
Panitumumab Results and Author Conclusions* High IHCLower IHCAll Patients ORR (%)7149 Median PFS (wks) Median OS (wks)4038 Gr 3/4 Skin Toxicity (%) 7 Panitumumab is active, not differing depending on EGFR status Panitumumab is well-tolerated *
Panitumumab Results and Author Conclusions* High IHCLower IHCAll Patients ORR (%)7149 Median PFS (wks) Median OS (wks)4038 Gr 3/4 Skin Toxicity (%) 7 Panitumumab is active, not differing depending on EGFR status Panitumumab is well-tolerated *
Panitumumab Results and Author Conclusions* High IHCLower IHCAll Patients ORR (%)7149 Median PFS (wks) Median OS (wks)4038 Gr 3/4 Skin Toxicity (%) 7 Panitumumab is active, not differing depending on EGFR status Panitumumab is well-tolerated *
Panitumumab Results and Author Conclusions* High IHCLower IHCAll Patients ORR (%)7149 Median PFS (wks) Median OS (wks)4038 Gr 3/4 Skin Toxicity (%) 7 Panitumumab is active, not differing depending on EGFR status Panitumumab is well-tolerated *
Panitumumab Results and Author Conclusions* High IHCLower IHCAll Patients ORR (%)7149 Median PFS (wks) Median OS (wks)4038 Gr 3/4 Skin Toxicity (%) 7 Panitumumab is active, not differing depending on EGFR status Panitumumab is well-tolerated *
Panitumumab Results and Author Conclusions* High IHCLower IHCAll Patients ORR (%)7149 Median PFS (wks) Median OS (wks)4038 Gr 3/4 Skin Toxicity (%) 7 Panitumumab is active, not differing depending on EGFR status Panitumumab is well-tolerated *
Panitumumab Commentary Panitumumab does appear active in pre-treated CRC In different populations, ORR of 9% and OS of 38 weeks seem roughly comparable to cetuximab Level of EGFR staining does not seem to predict activity –Non-expressers not tested on this trial There are multiple potential settings in which to test this antibody
Panitumumab Commentary Panitumumab does appear active in pre-treated CRC In different populations, ORR of 9% and OS of 38 weeks seem roughly comparable to cetuximab Level of EGFR staining does not seem to predict activity –Non-expressers not tested on this trial There are multiple potential settings in which to test this antibody
Panitumumab Commentary Panitumumab does appear active in pre-treated CRC In different populations, ORR of 9% and OS of 38 weeks seem roughly comparable to cetuximab Level of EGFR staining does not seem to predict activity –Non-expressers not tested on this trial There are multiple potential settings in which to test this antibody
Panitumumab Commentary Panitumumab does appear active in pre-treated CRC In different populations, ORR of 9% and OS of 38 weeks seem roughly comparable to cetuximab Level of EGFR staining does not seem to predict activity –Non-expressers not tested on this trial There are multiple potential settings in which to test this antibody
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Overall Conclusions CD Blanke, MD: Liar extraordinaire FOLFOX and FOLFIRI excellent upfront chemotherapeutic choices –IROX slightly less so It is reasonable in selected patients to start with 5FU alone and add irinotecan or oxaliplatin later –Not a good strategy for many (?most) subpopulations –Many patients will not ultimately receive all 3 drugs using this strategy
Conclusions (cont.) Oxaliplatin and irinotecan are both effective salvage agents –Oxali may be slightly better –Question remains: FOLFIRI or single-agent irinotecan Bevacizumab enhances FOLFOX and irinotecan- containing regimens, first- and second-line Panitumumab appears promising in late-line therapy of colorectal cancer
Conclusions (cont.) Oxaliplatin and irinotecan are both effective salvage agents –Oxali may be slightly better –Question remains: FOLFIRI or single-agent irinotecan Bevacizumab enhances FOLFOX and irinotecan- containing regimens, first- and second-line Panitumumab appears promising in late-line therapy of colorectal cancer
Conclusions (cont.) Oxaliplatin and irinotecan are both effective salvage agents –Oxali may be slightly better –Question remains: FOLFIRI or single-agent irinotecan Bevacizumab enhances FOLFOX and irinotecan- containing regimens, first- and second-line Panitumumab appears promising in late-line therapy of colorectal cancer
Conclusions (cont.) Oxaliplatin and irinotecan are both effective salvage agents –Oxali may be slightly better –Question remains: FOLFIRI or single-agent irinotecan Bevacizumab enhances FOLFOX and irinotecan- containing regimens, first- and second-line Panitumumab appears promising in late-line therapy of colorectal cancer
Conclusions (cont.) Oxaliplatin and irinotecan are both effective salvage agents –Oxali may be slightly better –Question remains: FOLFIRI or single-agent irinotecan Bevacizumab enhances FOLFOX and irinotecan- containing regimens, first- and second-line Panitumumab appears promising in late-line therapy of colorectal cancer
Colleagues…………………..………
Colorectal cancer is hot!