Transcript Patterns of Care in Medical Oncology

Patterns of Care in
Medical Oncology
Treatment of Metastatic Colon Cancer
Which systemic therapy is your typical first-line
choice for a chemotherapy-naïve patient with
metastatic colon cancer in otherwise average health
at the following ages?
65-year-old patient
FOLFOX + 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 first-line
choice for a chemotherapy-naïve patient with
metastatic colon cancer in otherwise average health
at the following ages? (continued)
85-year-old patient
FOLFOX + 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%
Clinical investigators
Practicing oncologists
Do you generally check the K-ras mutation status of
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%
Clinical investigators
Practicing oncologists
CRYSTAL trial: A Phase III randomized study of
FOLFIRI with or without cetuximab as first-line
therapy for EGFR-expressing metastatic colorectal
cancer
Efficacy
FOLFIRI +
cetuximab
(n = 599)
FOLFIRI
(n = 599)
p-value
Median PFS
8.9 months
8.0 months
0.048
34%
23%
—
46.9%
38.7%
0.0038
One-year PFS
rate
Overall
response
rate*
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
FOLFIRI with or without cetuximab as first-line
therapy for EGFR-expressing metastatic colorectal
cancer (continued)
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%
Safety: Grade III/IV
adverse events
† No
Grade IV skin reactions
Source: Van Cutsem E et al. Proc ASCO 2007;Abstract 4000.
Which systemic therapy would be your typical firstline choice for a chemotherapy-naïve patient with
metastatic colon cancer that is K-ras wild type?
65-year-old patient
FOLFOX + 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%
Clinical investigators
Practicing oncologists
Which systemic therapy would be your typical firstline choice for a chemotherapy-naïve patient with
metastatic colon cancer that is K-ras wild type?
(continued)
85-year-old patient
FOLFOX + 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%
Clinical investigators
Practicing oncologists
Which systemic therapy would be your typical firstline choice for a chemotherapy-naïve patient with
metastatic colon cancer that is mutant K-ras?
65-year-old patient
FOLFOX + 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%
Clinical investigators
Practicing oncologists
Which systemic therapy would be your typical firstline choice for a chemotherapy-naïve patient with
metastatic colon cancer that is mutant K-ras?
(continued)
85-year-old patient
FOLFOX + 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%
Clinical investigators
Practicing oncologists
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
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%
Clinical investigators
Practicing oncologists
Trial evaluating the benefit of perioperative
FOLFOX4 for patients with potentially resectable
colorectal cancer hepatic metastases
Protocol ID: EORTC-40983; Accrual: 364 (Closed)
FOLFOX4 x 6  surgery  FOLFOX4 x 6
R
Surgery
Source: Nordlinger B et al. Lancet 2008;371(9617):1007-16. Abstract
Trial evaluating the benefit of perioperative
FOLFOX4 for patients with potentially resectable
colorectal cancer hepatic metastases (continued)
Three-year
progression-free
survival
All patients
randomly assigned
(n = 182, 182)
All patients who
underwent
resection (n = 152,
151)
Reversible
postoperative
complications
(n = 159, 170)
Perioperative
FOLFOX4 +
surgery
Surgery
alone
HR (95.66% CI)
p-value
28.1%
0.79
(0.62-1.02)
0.058
42.4%
33.2%
0.73
(0.55-0.97)
0.025
25%
16%
—
0.04
35.4%
HR = hazard ratio; CI = confidence interval
Source: Nordlinger B et al. Lancet 2008;371(9617):1007-16. Abstract
For patients with colon cancer and liver metastases
that are surgically removed, which postoperative
treatment option would you most likely recommend
for the patients who have received no prior
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%
Clinical investigators
Practicing oncologists
Approximately how many patients per year do you
evaluate who have colorectal cancer with potentially
resectable hepatic metastases?
21
Median
Clinical investigators
Practicing oncologists
6
Case 3: 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)
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?
2008
Preop 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%
Clinical investigators
Practicing oncologists
Case 3: Metastatic Colon Cancer, No Prior
Systemic Therapy (continued)




A 65-year-old patient in otherwise average health
Three years ago, treated for Stage II sigmoid cancer (no
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?
2008
Resection of liver mets
0%
3%
Preop systemic therapy  resection
0%
0%
Other
4%
1%
Clinical investigators
Practicing oncologists
Case 3: Metastatic Colon Cancer, No Prior
Systemic Therapy (continued)




A 65-year-old patient in otherwise average health
Three years ago, treated for Stage II sigmoid cancer (no
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?
2005
Preop 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
Case 3: Metastatic Colon Cancer, No Prior
Systemic Therapy (continued)




A 65-year-old patient in otherwise average health
Three years ago, treated for Stage II sigmoid cancer (no
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?
2005
Resection of liver mets
0%
Preop systemic therapy  resection
9%
Other
10%
Practicing oncologists
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
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%
Clinical investigators
Practicing oncologists
Phase III randomized study of cetuximab and/or
bevacizumab in combination with either FOLFOX
or FOLFIRI
Protocol IDs: CALGB-C80405, C80405, SWOG-C80405, NCT00265850
Target Accrual: 2,300 (Temporarily Closed)
Chemotherapy + cetuximab
Eligibility
Previously untreated
metastatic
adenocarcinoma
of the colon or rectum
R
Chemotherapy +
cetuximab/bevacizumab
Chemotherapy + bevacizumab
Source: NCI Physician Data Query, December 2008.
Chemotherapy-free intervals are a reasonable
option when treating a patient with FOLFOX for
metastatic colon cancer.
Strongly agree
24%
17%
Agree
32%
53%
In between
20%
18%
Disagree
20%
12%
Strongly disagree
4%
0%
Clinical investigators
Practicing oncologists
With informed patient consent, it is reasonable to
use bevacizumab for patients with advanced
disease who have stable, treated brain metastases.
Agree
80%
57%
In between
0%
26%
Disagree
20%
17%
Clinical investigators
Practicing oncologists
Assume your patient is being treated with FOLFOX
or FOLFIRI, with bevacizumab. When utilizing
“planned drug holidays” to minimize toxicity in the
management of metastatic disease, do you
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%
Clinical investigators
Practicing oncologists
Patients who demonstrate significant responses
to FOLFOX/bevacizumab or FOLFIRI/bevacizumab
should have planned discontinuation of
oxaliplatin or irinotecan prior to the development
of significant toxicity.
Agree
64%
55%
In between
16%
35%
Disagree
20%
10%
Clinical investigators
Practicing oncologists
For a patient who demonstrates stable disease
on FOLFOX/bevacizumab and who is then
continued on bevacizumab alone, how long do
you generally continue bevacizumab if the patient
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%
Clinical investigators
Practicing oncologists
A 60-year-old patient has an excellent response to
FOLFOX + bevacizumab as first-line therapy for
metastatic disease and is continued on
bevacizumab. At 14 months, the patient develops
slow but definite disease progression. Outside of a
protocol setting, the bevacizumab should generally
be continued with the addition of another
agent/regimen.
Agree
60%
52%
In between
12%
27%
Disagree
28%
21%
Clinical investigators
Practicing oncologists
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
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%
* CI:
FOLFIRI + bevacizumab 28%; FOLFIRI + cetuximab 4%
PO: FOLFIRI + bevacizumab 31%; FOLFIRI + cetuximab 21%
Clinical investigators
Practicing oncologists
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
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%
Clinical investigators
Practicing oncologists
Approximately how many patients with metastatic
colon cancer have you treated with panitumumab?
12
Median
3
Approximately how many patients with metastatic colon
cancer have you treated with cetuximab?
111
Median
13
Of the patients with metastatic colon cancer you have treated
with cetuximab, approximately how many have developed
significant infusion reactions?
3
Median
Clinical investigators
Practicing oncologists
2
The severity of skin toxicity in patients undergoing
treatment with EGFR inhibitors such as cetuximab
and panitumumab correlates with response.
Agree
88%
61%
In between
8%
31%
Disagree
4%
8%
Clinical investigators
Practicing oncologists
How often do you use a regimen that
contains cetuximab with bevacizumab or
panitumumab with bevacizumab for patients
with metastatic colon cancer?
Very frequently
0%
4%
Frequently
0%
13%
Sometimes
24%
12%
Rarely
36%
25%
Never
40%
46%
Clinical investigators
Practicing oncologists