Patterns of Care in Medical Oncology Treatment of Metastatic Colon Cancer

Patterns of Care in Patterns of Care in Medical OncologyMedical Oncology

Treatment of Metastatic Colon Cancer

Which systemic therapy is your typical Which systemic therapy is your typical first-line first-line choice for a choice for a chemotherapy-naïvechemotherapy-naïve patient with patient with

metastatic colon cancer in otherwise average health metastatic colon cancer in otherwise average health at the following ages?at the following ages?

65-year-old patientFOLFOX + bevacizumab 76% 77%FOLFIRI + bevacizumab 16% 5%XELOX/CAPOX + bevacizumab 8% 3%FOLFOX 0% 7%Other 0% 8%

Clinical investigators Practicing oncologists

Which systemic therapy is your typical Which systemic therapy is your typical first-linefirst-line choice for a choice for a chemotherapy-naïvechemotherapy-naïve patient with patient with

metastatic colon cancer in otherwise average health metastatic colon cancer in otherwise average health at the following ages? (continued)at the following ages? (continued)

85-year-old patientFOLFOX + bevacizumab 40% 22%FOLFOX ± cetuximab 20% 8%Capecitabine ± bevacizumab* 24% 33%5-FU/LV ± bevacizumab† 12% 26%XELOX/CAPOX ± bevacizumab 4% 4%FOLFIRI + bevacizumab 0% 5%No systemic therapy 0% 2%


* CI = capecitabine alone 12%; capecitabine + bevacizumab 12%;PO = capecitabine alone 22%; capecitabine + bevacizumab 11%† CI = 5-FU/LV + bevacizumab 8%; 5-FU/LV alone 4%;PO = 5-FU/LV + bevacizumab 20%; 5-FU/LV alone 6%

Do you generally check the Do you generally check the K-ras mutationK-ras mutation status of status of a tumor in patients with metastatic colon cancer?a tumor in patients with metastatic colon cancer?

Yes 96% 38%No 0% 17%No, but I plan to 4% 45%

If yes, approximately when did you begin checking this?Prior to Dec 2007 0% 6%

Jan-Feb 2008 25% 0%

March-April 2008 17% 5%

May-June 2008 37% 39%

July-August 2008 21% 45%

Sept 2008-present 0% 5%


CRYSTAL trial: A Phase III randomized study of CRYSTAL trial: A Phase III randomized study of FOLFIRI with or without cetuximab as first-line FOLFIRI with or without cetuximab as first-line

therapy for EGFR-expressing metastatic colorectaltherapy for EGFR-expressing metastatic colorectalcancercancer

Efficacy

FOLFIRI + cetuximab(n = 599)

FOLFIRI(n = 599) p-value

Median PFS 8.9 months 8.0 months 0.048One-year PFS rate 34% 23% —Overall response rate* 46.9% 38.7% 0.0038

PFS = progression-free survival* Complete response + partial response

Source: Van Cutsem E et al. Proc ASCO 2007;Abstract 4000.

CRYSTAL trial: A Phase III randomized study of CRYSTAL trial: A Phase III randomized study of FOLFIRI with or without cetuximab as first-line FOLFIRI with or without cetuximab as first-line

therapy for EGFR-expressing metastatic colorectaltherapy for EGFR-expressing metastatic colorectalcancer (continued)cancer (continued)

† No Grade IV skin reactions

Source: Van Cutsem E et al. Proc ASCO 2007;Abstract 4000.

Safety: Grade III/IV adverse events

FOLFIRI + cetuximab(n = 600)

FOLFIRI(n = 602)

Neutropenia 26.7% 23.3%Diarrhea 15.2% 10.5%Skin reactions† 18.7% 0.2%Infusion related 2.3% 0%

Which systemic therapy would be your typical Which systemic therapy would be your typical first-first-lineline choice for a choice for a chemotherapy-naïvechemotherapy-naïve patient with patient with metastatic colon cancer that is K-ras wild type?metastatic colon cancer that is K-ras wild type?

65-year-old patientFOLFOX + bevacizumab 76% 62%FOLFIRI + bevacizumab 16% 5%XELOX/CAPOX + bevacizumab 8% 5%FOLFOX + cetuximab 0% 12%FOLFOX 0% 5%FOLFIRI + cetuximab 0% 5%Other systemic therapy 0% 6%


Which systemic therapy would be your typical Which systemic therapy would be your typical first-first-lineline choice for a choice for a chemotherapy-naïvechemotherapy-naïve patient with patient with metastatic colon cancer metastatic colon cancer that is K-ras wild type?

(continued)(continued)

85-year-old patientFOLFOX + bevacizumab 40% 13%Capecitabine ± bevacizumab 24% 30%FOLFOX 16% 5%5-FU/LV ± bevacizumab 12% 26%FOLFOX + cetuximab 4% 7%FOLFIRI + biologic* 0% 10%Other systemic therapy 4% 7%No systemic therapy 0% 2%


* PO: FOLFIRI + bevacizumab 6%; FOLFIRI + cetuximab 4%

Which systemic therapy would be your typical Which systemic therapy would be your typical first-first-lineline choice for a choice for a chemotherapy-naïvechemotherapy-naïve patient with patient with

metastatic colon cancer that is mutant K-ras?metastatic colon cancer that is mutant K-ras?

65-year-old patientFOLFOX + bevacizumab 76% 68%FOLFOX ± cetuximab 0% 14%FOLFIRI ± biologic* 16% 8%XELOX/CAPOX ± bevacizumab 8% 5%Capecitabine 0% 2%5-FU/LV + bevacizumab 0% 2%FOLFOXIRI 0% 1%


* CI: FOLFIRI + bevacizumab 16%; PO: FOLFIRI + bevacizumab 5%;FOLFIRI 2%; FOLFIRI + cetuximab 1%

Which systemic therapy would be your typical Which systemic therapy would be your typical first-first-lineline choice for a choice for a chemotherapy-naïvechemotherapy-naïve patient with patient with

metastatic colon cancer that is mutant K-ras? metastatic colon cancer that is mutant K-ras? (continued)(continued)

85-year-old patientFOLFOX + bevacizumab 40% 16%Capecitabine ± bevacizumab 24% 36%FOLFOX 20% 7%5-FU/LV ± bevacizumab 12% 25%XELOX/CAPOX ± bevacizumab 4% 3%FOLFIRI + biologic† 0% 7%Other systemic therapy 0% 4%No systemic therapy 0% 2%


† PO: FOLFIRI + bevacizumab 4%; FOLFIRI + cetuximab 3%

Which of the following treatment strategies, if any, are you most likely to recommend for this patient with colon cancer?Resection of liver mets systemic therapy 60% 50%Preop systemic therapy resection systemic therapy 24% 35%

Periop systemic therapy with 1/2 of cycles prior to resection and 1/2 after 16% 12%

Immediate resection of liver mets alone, no postop systemic therapy 0% 3%


Case 2: Metastatic Colon Cancer, No Prior Systemic Therapy

A 65-year-old patient in otherwise average health Three years ago, treated for Stage II sigmoid cancer (no

adjuvant chemotherapy) Now with 2 metastases in right lobe of liver that are considered

to be surgically resectable (maximum diameter 3 centimeters) No evidence of extrahepatic metastases

Trial evaluating the benefit of perioperative Trial evaluating the benefit of perioperative FOLFOX4 for patients with potentially resectable FOLFOX4 for patients with potentially resectable

colorectal cancer hepatic metastasescolorectal cancer hepatic metastases

Surgery

FOLFOX4 x 6 surgery FOLFOX4 x 6

Protocol ID: EORTC-40983; Accrual: 364 (Closed)

R

Source: Nordlinger B et al. Lancet 2008;371(9617):1007-16. Abstract

Trial evaluating the benefit of perioperative Trial evaluating the benefit of perioperative FOLFOX4 for patients with potentially resectable FOLFOX4 for patients with potentially resectable colorectal cancer hepatic metastases (continued)colorectal cancer hepatic metastases (continued)

HR = hazard ratio; CI = confidence interval

Source: Nordlinger B et al. Lancet 2008;371(9617):1007-16. Abstract

Three-year progression-free survival

Perioperative FOLFOX4 +

surgerySurgery

alone HR (95.66% CI) p-valueAll patients randomly assigned (n = 182, 182) 35.4% 28.1%

0.79(0.62-1.02) 0.058

All patients who underwent resection (n = 152, 151) 42.4% 33.2%

0.73(0.55-0.97) 0.025

Reversible postoperative complications (n = 159, 170) 25% 16% — 0.04

For patients with colon cancer and liver metastases For patients with colon cancer and liver metastases that are surgically removed, which postoperative that are surgically removed, which postoperative

treatment option would you most likely recommend treatment option would you most likely recommend for the patients who have received no prior for the patients who have received no prior

chemotherapy?chemotherapy?FOLFOX + bevacizumab 60% 67%FOLFOX 32% 17%XELOX/CAPOX + bevacizumab 8% 1%FOLFOX + cetuximab 0% 4%XELOX/CAPOX 0% 3%No systemic therapy 0% 2%Other 0% 6%


Approximately how many patients per year do you Approximately how many patients per year do you evaluate who have colorectal cancer with evaluate who have colorectal cancer with

potentially resectable hepatic metastases?potentially resectable hepatic metastases?

Median 21 6


2008Preop systemic therapy resection systemic therapy 76% 71%

Periop systemic therapy, 1/2 cycles prior to resection and 1/2 after 12% 13%

Systemic therapy alone 4% 6%Resection of liver mets systemic therapy 4% 6%


Case 3: Metastatic Colon Cancer, No Prior Systemic Therapy


adjuvant chemotherapy) CT scan reveals 6 metastases in both lobes of liver (5/8

liver segments affected) No evidence of extrahepatic metastases

Which treatment strategies, if any, are you most likely to recommend for this patient?

2008Resection of liver mets 0% 3%Preop systemic therapy resection 0% 0%Other 4% 1%


Case 3: Metastatic Colon Cancer, No Prior Systemic Therapy (continued)





2005Preop systemic therapy resection systemic therapy 0%Periop systemic therapy, 1/2 cycles prior to resection and 1/2 after 0%

Systemic therapy alone 79%Resection of liver mets systemic therapy 2%

Practicing oncologists






2005Resection of liver mets 0%

Preop systemic therapy resection 9%

Other 10%






Practicing oncologists

Which systemic therapy, if any, are you most likely to recommend for this patient?FOLFIRI + bevacizumab 68% 50%FOLFIRI 12% 6%FOLFOX + bevacizumab 4% 28%XELOX/CAPOX + bevacizumab 4% 3%Irinotecan + cetuximab 4% 1%Other 8% 12%


Case 4: Metastatic Colon Cancer, Previous Adjuvant Treatment

A 65-year-old patient in otherwise average health One year ago, completed treatment for a Stage III lesion with resection and

adjuvant FOLFOX (5-FU + leucovorin + oxaliplatin) chemotherapy for 6 months

Now presents with 12 liver metastases

Chemotherapy + bevacizumab

Chemotherapy + cetuximab

Protocol IDs: CALGB-C80405, C80405, SWOG-C80405, NCT00265850Target Accrual: 2,300 (Temporarily Closed)

Eligibility

Previously untreatedmetastatic adenocarcinomaof the colon or rectum

Phase III randomized study of cetuximab and/or Phase III randomized study of cetuximab and/or bevacizumab in combination with either FOLFOX bevacizumab in combination with either FOLFOX

or FOLFIRIor FOLFIRI

Source: NCI Physician Data Query, December 2008.

Chemotherapy + cetuximab/bevacizumabR

Chemotherapy-free intervals are a reasonable Chemotherapy-free intervals are a reasonable option when treating a patient with FOLFOX for option when treating a patient with FOLFOX for

metastatic colon cancer.metastatic colon cancer.

Strongly agree 24% 17%Agree 32% 53%In between 20% 18%Disagree 20% 12%Strongly disagree 4% 0%


With informed patient consent, it is reasonable to With informed patient consent, it is reasonable to use bevacizumab for patients with advanced use bevacizumab for patients with advanced

disease who have stable, treated brain metastases.disease who have stable, treated brain metastases.

Agree 80% 57%In between 0% 26%Disagree 20% 17%


Assume your patient is being treated with FOLFOX Assume your patient is being treated with FOLFOX or FOLFIRI, with bevacizumab. When utilizing or FOLFIRI, with bevacizumab. When utilizing

“planned drug holidays” to minimize toxicity in the “planned drug holidays” to minimize toxicity in the management of metastatic disease, do you management of metastatic disease, do you

routinely:routinely:Discontinue the oxali/irinotecan component only (maintaining fluoropyrimidine and bev) 64% 45%

Completely discontinue all medical treatment (chemo-free interval) 28% 26%

Discontinue all chemo (maintaining bev only) 0% 24%Discontinue the oxali/irinotecan and bev components (maintaining fluoropyrimidine only) 0% 5%

Other 8% 0%


Patients who demonstrate significant responses Patients who demonstrate significant responses to FOLFOX/bevacizumab or FOLFIRI/bevacizumab to FOLFOX/bevacizumab or FOLFIRI/bevacizumab

should have planned discontinuation of should have planned discontinuation of oxaliplatin or irinotecan prior to the development oxaliplatin or irinotecan prior to the development

of significant toxicity.of significant toxicity.



For a patient who demonstrates stable disease For a patient who demonstrates stable disease on FOLFOX/bevacizumab and who is then on FOLFOX/bevacizumab and who is then

continued on bevacizumab alone, how long do continued on bevacizumab alone, how long do you generally continue bevacizumab if the patient you generally continue bevacizumab if the patient

is tolerating it well?is tolerating it well?I don’t use maintenance bev 60% 17%Until disease progression 32% 68%A specified number of cycles 4% 13%Other 4% 2%


A 60-year-old patient has an excellent response to A 60-year-old patient has an excellent response to FOLFOX + bevacizumab as first-line therapy for FOLFOX + bevacizumab as first-line therapy for

metastatic disease and is continued on metastatic disease and is continued on bevacizumab. At 14 months, the patient develops bevacizumab. At 14 months, the patient develops

slow but definite disease progression. Outside of a slow but definite disease progression. Outside of a protocol setting, the bevacizumab should generally protocol setting, the bevacizumab should generally

be continued with the addition of another be continued with the addition of another agent/regimen.agent/regimen.



Which systemic therapy, if any, are you most likely to recommend as second-line therapy for this patient?Irinotecan ± cetuximab 52% 19%FOLFIRI + biologic* 32% 52%FOLFIRI alone 8% 17%Chemotherapy + panitumumab 4% 1%


Case 5: Second-Line Treatment for Metastatic Colon Cancer

A 65-year-old patient in otherwise average health Received FOLFOX (5-FU + leucovorin + oxaliplatin) + bevacizumab as first-

line therapy for 6 months for hepatic metastases Demonstrates a partial response, then develops subsequent pulmonary

metastases and progression of hepatic metastases

* CI: FOLFIRI + bevacizumab 28%; FOLFIRI + cetuximab 4%PO: FOLFIRI + bevacizumab 31%; FOLFIRI + cetuximab 21%

Which systemic therapy, if any, are you most likely to recommend as second-line therapy for this patient?Capecitabine ± bevacizumab 0% 5%XELOX/CAPOX ± bevacizumab 0% 5%Other 4% 1%


Case 5: Second-Line Treatment for Metastatic Colon Cancer (continued)

A 65-year-old patient in otherwise average health Received FOLFOX (5-FU + leucovorin + oxaliplatin) + bevacizumab as first-

line therapy for 6 months for hepatic metastases Demonstrates a partial response, then develops subsequent pulmonary

metastases and progression of hepatic metastases

Approximately how many patients with metastatic Approximately how many patients with metastatic colon cancer have you treated with panitumumab?colon cancer have you treated with panitumumab?

Median 12 3

Approximately how many patients with metastatic colon cancer have you treated with cetuximab?Median 111 13

Of the patients with metastatic colon cancer you have treated with cetuximab, approximately how many have developed significant infusion reactions?Median 3 2


The severity of skin toxicity in patients undergoing The severity of skin toxicity in patients undergoing treatment with EGFR inhibitors such as cetuximab treatment with EGFR inhibitors such as cetuximab

and panitumumab correlates with response.and panitumumab correlates with response.



How often do you use a regimen that How often do you use a regimen that contains cetuximab with bevacizumab or contains cetuximab with bevacizumab or

panitumumab with bevacizumab for patients panitumumab with bevacizumab for patients with metastatic colon cancer?with metastatic colon cancer?

Very frequently 0% 4%Frequently 0% 13%Sometimes 24% 12%Rarely 36% 25%Never 40% 46%


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Patterns of Care in Medical Oncology Treatment of Metastatic Colon Cancer