Tratamiento de cáncer de colon metastásico: de las guías de práctica, genómica, a la práctica clínica.

1. Tratamiento del cáncer colorectal metastásico: de las guías
de práctica clínica, pasando por la genómica y la realidad
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín, Colombia
Cartagena, Colombia
09.07.2014

3. FULVFULV
CapecCapec
IriIri
BevBev
CetCet
PanPan
Regor.Regor.
SurgerySurgery
Ablative
Rx
Ablative
Rx
OxOx Aflib.Aflib. Ramuc.Ramuc.

5. FULVFULV BevBevCapecCapec BevBev
FULVFULVCapecCapec
FULVFULV OxOx IriIri

6. FULVFULV OxOx BevBev CapecCapec OxOx BevBev
FULVFULV OxOx IriIri BevBev FULVFULV OxOx
FULVFULV IriIri BevBev CapecCapec IriIri BevBev

7. FULVFULV OxOx CetCet CapecCapec OxOx CetCet
FULVFULV IriIri IriIri CetCet
FULVFULV IriIri CetCet CapecCapec IriIri CetCet
CetCet

8. FULVFULV OxOx PaniPani CapecCapec OxOx PaniPani
FULVFULV IriIri IriIri PaniPani
FULVFULV IriIri PaniPani CapecCapec IriIri PaniPani
PaniPani

9. FULVFULV OxOx AflibAflib CapecCapec OxOx AflibAflib
FULVFULV IriIri IriIri AflibAflib
FULVFULV IriIri AflibAflib CapecCapec IriIri AflibAflib

10. “Thou shall not use anti-EGFR agents
in mutated RAS CRC patients”

11. mCRC: ESMO Clinical Practice
Guidelines
http://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Metastatic-Colorectal-Cancer
Group 0Group 0
Group 1Group 1
Group 2Group 2
Group 3Group 3
Resectable R0
Convertible
Unlikely
resectable/High
tumor burden
Never resectable
Surgery/ +/- Adj CTSurgery/ +/- Adj CT
Conversion CT/SurgeryConversion CT/Surgery
Conversion CT/SurgeryConversion CT/Surgery
Less-toxic CTLess-toxic CT
Cure
Cure
Long OS
QoL
Criticism: solely based on DISEASE characteristics

12. mCRC: ESMO Clinical Practice
Guidelines
http://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Metastatic-Colorectal-Cancer
Group 0Group 0
Group 1Group 1
Group 2Group 2
Group 3Group 3
Resectable R0
Convertible
Unlikely
resectable/High
tumor burden
Never resectable
Surgery/ +/- Adj CTSurgery/ +/- Adj CT
Conversion CT/SurgeryConversion CT/Surgery
Active CT + BiologicActive CT + Biologic
Less-toxic CTLess-toxic CT
FOLFOX
FOLFOXIRI-Bev
FOLFIRI-Cet
FOLFOX-Bev
XELOX-Bev
FOLFOX-Cet
FOLFIRI-Cet
FP-Bev
Criticism: solely based on DISEASE characteristics

13. Do THESE guidelines, guide?

14. Let’s start with curative intent

15. Continuum of care
SurgerySurgery FULVFULV OxOx
FULVFULV OxOx IriIri SurgerySurgery
FULVFULV IriIri CetCet
SurgerySurgery

16. OS after resection in liver
metastasis
Adam R, Oncologist, 2012

17. OS after resection in liver
metastasis
Adam R, Oncologist, 2012

18. OS after resection in liver metastasis,
after preoperative chemotherapy
Adam R, Oncologist, 2012

19. FOLFIRINOX combined to targeted therapy according
RAS status for colorectal cancer patients with liver
metastases initially non-resectable: A phase II randomized
Study—Prodige 14 – accord 21 (METHEP-2), a unicancer
GI trial. Mark Ychou. Proc ASCO, 2016, Abstract 3512
Proc ASCO, 2016, Discussio
.
FOLFIRINOX as induction treatment in rectal cancer
patients with synchronous metastases (RCSM): Results of
the FFCD 1102 phase II trial. JB Bachet. Proc ASCO, 2016,
Abstract 3513

20. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

21. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

22. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

23. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

24. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

25. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

26. Is More Better?, Steven J Cohen
Proc ASCO, 2016, Discussio
.

27. THAT was easy, what about the
rest?

28. CAPOX +
Bevacizumab
6 meses
“Continuum of care” in mCRC – “blurring line descriptions”
Cape + Bevacizumab
Hasta progresión
1o
línea
FOLFIRI +
Bevacizumab
Oxaliplatino hasta neuropatía
QT + Bevacizumab
Hasta progresión
2o
línea
Cetuximab +/-
Irinotecán
Regorafenib
Hasta progresión
≥3o
línea (KRAS nativo)
Hasta progresión
CAIRO-3
TML
Cunningham D, et al. N Engl J Med 2004;351:337-45. CORRECT Trial (Van Cutsem 2012)

29. In the RAS wt, which first-line
agent?

30. clinicaloptions.com/oncology
Optimizing Treatment of Metastatic Colorectal Cancer
Mutations in KRAS, NRAS, and BRAF
Distribution and Prognostic Significance
BRAF mutation All patients
Any mutation
KRAS mutation
KRAS WT
All WT
Mutation Status
0
6
12
MedianPFS
(Mos)
Arm A Arm B
0
6
12
18
MedianOS
(Mos)
57
340
268
815
367
289
45
366
297
815
362
292
0
10
20
30
40
2-YrOS(%)
Prognostic Effect of Mutational Status
“All WT”
n = 581
(44%)
KRAS MT
n = 565
(43%)
NRAS MT
n = 50 (4%)
BRAF MT
n = 102 (8%)
Total
N = 1316 (81%)
554
11
39
10
2
Population n (%) Arm A Arm B
ITT 1630 815 815
Assessed for mutations 1316 648 668
 KRAS mutation
 NRAS mutation
 BRAF mutation
565 (43)
50 (4)
102 (8)
268
18
57
297
32
45
KRAS WT 729 (55) 367 362
KRAS/NRAS/BRAF WT
“All WT”
581 (44) 289 292
Maughan TS, et al. ASCO 2010. Abstract 3502.

31. clinicaloptions.com/oncology
Optimizing Treatment of Metastatic Colorectal Cancer
Phase III 80405 Trial: First-line CT + Either
Cetux or Bev in KRAS-WT mCRC
 Primary endpoint: OS
 Secondary endpoints: ORR, PFS, TTF, duration of response
Patients with mCRC
and KRAS WT
(codons 12, 13),
ECOG PS 0/1
(N = 1137)
FOLFOX or FOLFIRI +
Bevacizumab q2w
(n = 559)
ClinicalTrials.gov. NCT00265850. Venook AP, et al. ASCO 2014. LBA3..
FOLFOX or FOLFIRI +
Cetuximab q1w
(N = 578)
A third arm with CT + bevacizumab + cetuximab
was closed to accrual in September 2009

32. clinicaloptions.com/oncology
Optimizing Treatment of Metastatic Colorectal Cancer
CALGB/SWOG 80405: OS in the ITT
Population
mOS (95% CI), mos
CT + Cetux 29.9 (27.0-32.9)
CT + Bev 29.0 (25.7-31.2)
HR 0.925 (0.78-1.09)
P = 0.34
Venook AP, et al. ASCO 2014. Abstract LBA3.
0
12 24 36 48 60 72
Mos
80
100
60
40
0
OS(%)
20
84

33. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.

34. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.

35. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.

36. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.

37. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.

38. Impact of primary (1º) tumor location on overall survival
(OS) and progression-free survival (PFS) in patients (pts)
with metastatic colorectal cancer (mCRC): Analysis of
CALGB/SWOG 80405 (Alliance). Alan P. Venook.
Proc ASCO, 2016, 3504
.

39. The relationship between primary tumor sidedness and
prognosis in colorectal cancer. Deborah Schrag
Proc ASCO, 2016, 3505
.

40. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

41. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

42. Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee
Proc ASCO, 2016, 3505
.

43. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

44. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

45. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

46. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

47. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

48. Proc ASCO, 2016, 3505
.
Association of primary (1°) site and molecular features with
progression-free survival (PFS) and overall survival (OS) of
metastatic colorectal cancer (mCRC) after anti-epidermal
growth factor receptor ( EGFR) therapy. Michael Sangminα
Lee

49. Side Matters. Kimmie Ng
Proc ASCO, 2016, Dicussion
.

50. What should we do with BRAF
mutated mCRC?

51. FULVFULV OxOx IriIri BevBev
What about mBRAF mCRC?
• Not very clear
• TRIBE study suggests FOLFOXIRI-Bev(1)
• Further studies of anti-BRAF coupled with
other agents are expected (ie, Cetuximab).
1. Loupakis F, NEJM, 2014

52. Continuum of care in mCRC

53. Continuum of care
FULVFULV OxOx BevBev
What to do in second line?

54. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Phase III ML18147 (TML): Continuing
Bevacizumab Beyond Progression
Standard second-line CT
(oxaliplatin or irinotecan based) until PD
(n = 411)
Bevacizumab 2.5 mg/kg/wk +
standard second-line CT (oxaliplatin or
irinotecan-based) until PD
(n = 409)
Progressive mCRC after
BEV + standard first-line
CT (either oxaliplatin or
irinotecan based)
(n = 820)
Bennouna J, et al. Lancet Oncol. 2013;14:29-37.
Stratified by first-line CT (oxaliplatin or irinotecan
based), first-line PFS (≤ 9 vs > 9 mos), time
from last BEV dose (≤ 42 vs > 42 days),
ECOG PS at baseline (0/1 vs 2)
 Primary endpoint: OS
 Secondary endpoints: PFS, ORR, safety

55. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Continuing Bevacizumab Beyond
Progression (TML): OS, PFS
OS(%)
Mos
CT (n = 410)
BEV + CT (n = 409)
100
80
60
40
20
0
0 6 12 18 24 30 36 42
48
9.8 mos9.8 mos 11.2 mos11.2 mos
Unstratified* HR: 0.81 (95% CI:
0.69-0.94; log-rank P = .0062)
Stratified†
HR: 0.83 (95% CI:
0.71-0.97; log-rank P = .0211)
*Primary analysis method. †
Stratified by first-line CT (oxaliplatin based, irinotecan based), first-line PFS
(≤ 9 mos, > 9 mos), time from last dose of BEV (≤ 42 days, > 42 days), ECOG PS at baseline (0, ≥ 1).
Bennouna J, et al. Lancet Oncol. 2013;14:29-37.
100
80
60
40
20
0
PFS(%) 0 6 12 18 24 30 36 42
Mos
Unstratified* HR: 0.68 (95% CI:
0.59-0.78; log-rank P < .0001)
Stratified†
HR: 0.67 (95% CI: 0.58-
0.78; log-rank P < .0001)
4.1mo4.1mo
5.7 mo5.7 mo
Overall Survival Progression-Free Survival

56. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Phase III VELOUR Study: FOLFIRI ± ziv-
Aflibercept as Second-line Therapy in mCRC
 Primary endpoint: OS
 Secondary endpoints: PFS, ORR, safety, immunogenicity
 No correlatives
Patients with mCRC
progressing on first-line
oxaliplatin-based
chemotherapy*
(planned N = 1226)
FOLFIRI + ziv-Aflibercept 4 mg/kg q2w
(n = 612)
FOLFIRI + Placebo q2w
(n = 614)
*30% had previous bevacizumab.
Stratified by previous bevacizumab (yes vs no),
ECOG PS (0 vs 1 vs 2)
Van Cutsem E, et al. J Clin Oncol. 2012;30:3499-3506. ClinicalTrials.gov. NCT00561470.

57. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
FOLFIRI ± ziv-Aflibercept as Second-line
Therapy in mCRC (VELOUR): OS, PFS
Van Cutsem E, et al. J Clin Oncol. 2012;30:3499-3506.
Stratified HR: 0.817 (95.34% CI:
0.713-0.937; log-rank P = .0032)
Placebo/FOLFIRI
Median: 12.06 mos
Aflibercept/FOLFIRI
Median: 13.50 mos
PFS(%)
100
80
60
40
20
0
Mos
0 3 6 9 12 15 18 21 24 27 30
Stratified HR: 0.758 (95% CI: 0.661-
0.869; log-rank P < .0001)
Placebo/FOLFIRI
Median: 4.67 mos
Aflibercept/FOLFIRI
Median: 6.90 mos
Overall Survival Progression-Free Survival
OS(%)
100
80
60
40
20
0
Mos
0 3 6 9 12 15 18 21 24 27 30 33 36 39

58. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Tabernero J, et al. Eur J Cancer. 2014;50:320-331.
OS(%)
100
80
60
40
20
0
Mos
0 3 6 9 12 15 18 21 24 27 30 33 36 39
HR: 0.862 (95.34% CI: 0.673-1.104)
Placebo/FOLFIRI
Median: 11.7 mos
Aflibercept/FOLFIRI
Median: 12.5 mos
Pts at Risk, n
Placebo
AFL
187
186
170
178
138
150
115
121
81
89
54
59
37
36
22
22
13
13
Previous Bevacizumab
OS(%)
100
80
60
40
20
0
Mos
0 3 6 9 12 15 18 21 24 27 30 33 36 39
HR: 0.788 (95.34% CI: 0.699-0.927)
Placebo/FOLFIRI
Median: 12.4 mos
Aflibercept/FOLFIRI
Median: 13.9 mos
Pts at Risk, n
Placebo
AFL
427
426
403
388
347
348
286
295
205
222
139
157
94
112
65
82
38
62
No Previous Bevacizumab
2nd
-Line FOLFIRI ± ziv-Aflibercept in mCRC
(VELOUR): OS by Prior Bevacizumab

59. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Phase III RAISE Study: Second-Line
Ramucirumab/FOLFIRI vs FOLFIRI
Patients with CRC
and progression
during or within 6
months of first-line
bevacizumab,
oxaliplatin, and a
fluoropyrimidine
(N = 1072)
Treat until PD or
unacceptable
toxicity
Ramucirumab 8 mg/kg +
FOLFIRI q2w per cycle
(n = 536)
Placebo +
FOLFIRI q2w per cycle
(n = 536)
Stratified by geographic region, KRAS mutation
status, TTP after start of first-line therapy
 Ramucirumab: anti-VEGFR2 antibody
 Primary endpoint: OS
Tabernero J, et al. Lancet Oncol. 2015;16:499-508.

60. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Ramucirumab +
FOLFIRI
Placebo +
FOLFIRI
Median OS, mo
(95% CI)
13.3
(12.4-14.5)
11.7
(10.8-12.7)
HR (95% CI) 0.844 (0.73-0.976) (stratified)
P Value (log-rank) .0219 (stratified)
Second-Line Ramucirumab/FOLFIRI vs
FOLFIRI (RAISE): Overall Survival
Tabernero J, et al. Lancet Oncol. 2015;16:499-508.
497 345 195 78 34 12 0536 421 269 114 53 422 0
486 329 166 66 22 2 1536 400 228 108 44 210 0
Pts at Risk, n
Placebo +
FOLFIRI
Ram +
FOLFIRI
Ramucirumab + FOLFIRI
Placebo + FOLFIRI
OverallSurvival
0.2
0.4
0.6
0.8
1.0
0
0 6 12 18 24 30 3633 399 15 21 273 42
Mos

61. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev
LL
TML

62. OxOx Aflib.Aflib. Ramuc.Ramuc.
IriIri PanPan Ablative
Rx
Ablative
Rx
What to do when all else has failed?
CapecCapec CetCet SurgerySurgery
FULVFULV BevBev

63. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Inhibition of
neoangiogenesis
Inhibition of tumor
microenvironment
signaling
Inhibition of
proliferation
Regorafenib: Oral Multikinase Inhibitor
Targeting Multiple Tumor Pathways
Wilhelm SM, et al. Int J Cancer. 2011;129:245-255. Mross K, et al. Clin Cancer Res. 2012;18:2658-2667. Strumberg D, et
al. Expert Opin Invest Drugs. 2012;21:879-889.
KIT
PDGFR
RET
PDGFR-β
FGFR
VEGFR1-3
TIE2
RegorafenibF
Cl
F
F F
O
O
O
N
H
N
H
N
H
N
Biochemical
Activity
Regorafenib IC50
Mean ±SD nmol/L (n)
VEGFR1 13 ± 0.4 (2)
Murine VEGFR2 4.2 ± 1.6 (10)
Murine VEGFR3 46 ± 10 (4)
TIE2 311 ± 46 (4)
PDGFR-β 22 ± 3 (2)
FGFR1 202 ± 18 (6)
KIT 7 ± 2 (4)
RET 1.5 ± 0.7 (2)
RAF-1 2.5 ± 0.6 (4)
B-RAF 28 ± 10 (6)
B-RAFV600E
19 ± 6 (6)

64. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Phase III CORRECT: Regorafenib After
Failure of Standard Therapy in mCRC
 Primary endpoint: overall survival
 Prior systemic, anticancer therapies (palliative)
– 1-2 prior lines: 26%
– 3 prior lines: 26%
– ≥ 4 prior lines: 48%
Patients with
progression
after all
available
standard
therapy
(N = 760)
Arm A: Regorafenib 160 mg po qd + BSC
3 wks on, 1 wk off
(n = 505)
Arm B: Placebo + BSC
3 wks on, 1 wk off
(n = 255)
Grothey A, et al. Lancet. 2013;381:303-312.
2:1

65. clinicaloptions.com/oncology
Colorectal Cancer: Individualizing Therapy Beyond Second-line Treatment
Regorafenib After Failure of Standard
Therapy in mCRC (CORRECT): OS, PFS
Primary endpoint met prespecified stopping criteria at second interim analysis
(1-sided P ≤ .009279 at approximately 74% of events required for final analysis)
100
50
25
0
75
Mos From Randomization
OS(%)
HR: 0.77 (95% CI: 0.64-0.94;
P = .0052)
Regorafenib Placebo
Median OS, mo 6.4 5.0
IQR 3.6-11.8 2.8-10.4
Placebo (n = 255)
Regorafenib (n = 505)
Grothey A, et al. Lancet. 2013;381:303-312.
0 2 4 6 8 10 12 14
Regorafenib Placebo
Median PFS, mo 1.9 1.7
IQR 1.6-3.9 1.4-1.9
0 2 4 6 8 10 12
Mos From Randomization
100
50
25
0
75
PFS(%)
Placebo (n = 255)
Regorafenib (n = 505)
HR: 0.49 (95% CI: 0.42-0.58;
P < .0001 )
Overall Survival Progression-Free Survival

66. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev Regor.Regor.
LL
TML

67. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev Cetuxi.Cetuxi.
wtRAS(1)
2. Cunningham, D, NEJM, 2004

68. Continuum de tratamiento en mCRC no resecable
KRAS no mutado
Bev+CAPOX x6
Bev+Cap
Bev+CAPOX
FOLFIRI+Bev
Cet+/-Iri
Regorafenib
CAIRO-3 (2013) TML (2012) C0.17 (2008) CORRECT (2012)

69. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev Regor.Regor.
Capecitabina
Capecitabina
Capecitabina
Aflibercetp

70. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev Regor.Regor.
Capecitabina
Capecitabina
Capecitabina
Aflibercetp

71. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev Regor.Regor.
Capecitabina
Capecitabina
Capecitabina
Aflibercetp

72. Continuum of care
FULVFULV OxOx BevBev
FULVFULV OxOx BevBev
FULVFULV BevBev
FULVFULV IriIri BevBev Regor.Regor.
Capecitabina
Capecitabina
Capecitabina
Cetuxi
Cetuxi
Cetuxim

73. Continuum of care
KRAS mutated
Bev+CAPOX x6
Bev+Cap
Bev+CAPOX
FOLFIRI+Bev
Regorafenib

74. What about patient related
issues?
What to do with a patient only able
to tolerate some chemo.

75. Continuum of care
KRAS wt, un-fit
Bev+Cap
Bev+FOLFOX
FOLFIRI+Bev
Cet+/-Iri
Regorafenib
AVEX (2013)

76. Continuum of care
KRAS mutated, un-fit
Bev+Cap
Bev+FOLFOX
FOLFIRI+Bev
Regorafenib

77. Do THESE guidelines, guide?
Maybe, but a more comprehensive
strategy NEEDS to be thought –out
BEFORE therapy initiation.

78. Conclusions
Clinical presentation
Treatment toolkit
Rules of engagement
What WE desire
Patient preference
Tumor biology
Cost
Patient access

79. As of today, clinical practice
guidelines for mCRC are but a
repository of treatment options
filled with soft statements aimed
more to convince insurers rather
than to truly guide clinicians.