Proposed Pathway & Evidence for Colorectal Profiler– UPDATE IN PROGRESS

Adjuvant Stage III Colon Cancer

NCCN:

Category 1: mFOLFOX & mFLOX

Category 2a: simp 5FU/Leu, 5FU/Leu, Capecitabine alone, CapeOx

Adjuvant Stage III Colon Cancer

Pathway Preference / Regimen / Evidence / Cost
Clinic Margin
1 / mFOLFOX /
  • MOSAIC trial showed superiority over simp 5FU/Leu in DFS, in overall survival showed slight superiority with HR of 0.8
/ $X
$X
2 / Simp 5FU/Leu /
  • For patients who cannot tolerate oxaliplatin
/ $X
$X
3 / 5FU/Leu /
  • Not studied against mFOLFOX
  • Equivalent but less expensive than Capecitabine alone
/ $X
$X
3 / Capecitabine alone /
  • Twelves 2005 study showed equivalency to bolus 5FU/Leu in DFS, overall survival and relapse free survival
/ $X
$X
3 / CapeOx /
  • No study showing equivalency or superiority to a 5FU/Leu regimen or mFOLFOX, does have a study showing similar safety profile as Cape
/ $X
$X
NP+ / mFLOX /
  • NSABP C-07 Trial showed superiority over bolus 5FU/Leu in disease free survival, but equivalency in overall survival. Also, if patients recur then their overall survival is worse with mFLOX over 5FU/Leu
  • Worse diarrhea over mFOLFOX
/ $X
$X

+NP = non-preferred

Adjuvant Stage II – III Rectal Cancer

NCCN:

Category 2a: all regimens

Category 2b: Capecitabine/RT

AdjuvantRectal Cancer – Concurrent Chemo/RT – 6 weeks

Pathway Preference / Regimen / Evidence / Cost
Clinic Margin
1 / Cont 5FU/RT /
  • O’Connell NEJM 1994 Study found that continuous infusion 5FU had a significantly longer time to relapse than bolus 5FU/Leuc (63% vs 53%, p=0.01) and significantly longer survival rate at 4 years (70% vs 60%, p=0.005).
/ $X
$X
2 / Capecitabine/RT /
  • Data is limited, no phase III studies exist (one is currently underway).
  • R04 Study (non-inferior trial) results presented at ASCO showed equivalency in over-all survival at 5 years to cont 5FU/RT, and mixed results in disease-free survival: 3-year DFS showing superiority.
  • More hand foot syndrome, proctitis & fatigue but less neutropenia than a 5FU/Leuc regimen.
/ $X
$X
3 / 5FU-Leuc/RT /
  • See cont 5FU/RT above.
/ $X
$X

AdjuvantRectal Cancer – Adjuvant Chemo (used after Concurrent Chemo/RT)

Pathway Preference / Regimen / Evidence / Cost
Clinic Margin
1 / mFOLFOX /
  • Data extrapolated from colon studies (see adjuvant colon above).
  • One studied evaluated versus 5FU-Leuc, but was stopped early to spend resources evaluating bevacizumab. The safety data found more grade 3/4 neutropenia (31% vs 4%) and less grade 3/4 diarrhea (4% vs 13%) when compared to 5FU-Leuc.
/ $X
$X
2 / 5FU-Leuc /
  • Extrapolated data from the metastatic colon studies.
  • See above about study that was stopped early.
/ $X
$X
3 / Capecitabine alone /
  • Data extrapolated from metastatic colon studies.
/ $X
$X
NP / CapeOx /
  • Data extrapolated from colon studies (see CapeOx above for adjuvant colon).
/ $X
$X

Metastatic Colorectal Cancer

NCCN:

Category 2a: All regimens below

Category 2b: FOLFOXIRI

Metastatic ColoRectal CancerKRAS Mutation

Pathway Preference / Regimen / Evidence / Cost
Clinic Margin
1 / FOLFIRI – Bevacizumab /
  • Phase IV study (200 patients) evaluating FOLFIRI+Bev showed similar outcomes to other Phase III studies of 5FU regimens + Bev (mFOLFOX). Median overall survival was 22.2 months.
  • Phase III study showed no difference between FOLFIRI and mFOLFOX in ORR (34% vs 36%), TTP (7 months for both arms) or OS (14 mo vs 15 mo).
/ $X
$X
2 / mFOLFOX6 – Bevacizumab /
  • TREE-2 Study found that mFOLFOX with bevacizumab had improved OS over mFOLFOX alone (26.1 months versus 19.2 months) and equivalent safety.
  • For patients who have failed FOLFIRI or cannot tolerate irinotecan.
/ $X
$X
3 / FOLFIRI /
  • For patients who have contraindications to bevacizumab (clotting, uncontrolled HTN, proteinuria) or who have failed a previous bevacizumab containing regimen.
  • See FOLFIRI+Bevacizumab
/ $X
$X
4 / mFOLFOX6 /
  • For patients that have failed FOLFIRI AND have contraindications to bevacizumab (clotting, uncontrolled HTN, proteinuria) or who have failed a previous bevacizumab containing regimen.
/ $X
$X
NP / 5FU/Leuc Weekly /
  • For patients who cannot tolerate aggressive chemotherapy
  • For patients who have contraindications to bevacizumab (clotting, uncontrolled HTN, proteinuria)
/ $X
$X
NP / Simp 5FU/Leuc /
  • For patients who cannot tolerate aggressive chemotherapy
  • For patients who have contraindications to bevacizumab (clotting, uncontrolled HTN, proteinuria)
/ $X
$X
NP / FOLFIRI – panitu-mumab /
  • No significant OS advantage was shown when EGFR inhibitors were added to chemotherapy (14.5 mo. FOLFIRI + panitumumab vs 12.5 mo. for FOLRIRI alone, p = 0.12) (Peeters et al JCO 2010)
  • Failed previous metastatic treatment
  • KRAS WT only
/ $X
$X
NP / FOLFIRI - cetuximab /
  • No statistically significant OS advantage was shown when EGFR inhibitors were added to chemotherapy (CRYSTAL Trial)
  • Failed previous metastatic treatment
  • KRAS WT only
/ $X
$X
NP / mFOLFOX6-panitumumab /
  • No statistically significant OS advantage shown when panitumumab was added to FOLFOX. (OS 23.9 mo for FOLFOX +panitumumab vs. 19.7 mo for FOLFOX alone, p = 0.072) (PRIME trial)
  • KRAS WT only
/ $X
$X
NP / mFOLFOX6 – cetuximab /
  • No OS advantage was shown when EGFR inhibitors were added to chemotherapy (Opus trial 22.8 months for FOLFOX + cetuximab vs. 18.5 months for FOLFOX alone, p = 0.39)
  • For patients who have failed previous metastatic treatment
  • KRAS WT only
  • Most expensive colorectal regimen
/ $X
$X
NP / Irinotecan alone /
  • For patients who cannot tolerate or have failed mFOLFOX and cannot tolerate FOLFIRI
/ $X
$X
NP / Irinotecan – cetuximab /
  • No OS advantage was shown when EGFR inhibitors were added to chemotherapy
  • For patients who have failed mFOLFOX or CapeOx (2B NCCN recommendation)
  • KRAS WT only
/ $X
$X
NP / Irinotecan – bevacizumab /
  • For patients who cannot tolerate aggressive chemotherapy
/ $X
$X
NP / Capecitabine alone /
  • For patients who cannot tolerate aggressive chemotherapy
  • Should NOT be used as salvage therapy
/ $X
$X
NP / Capecitabine – Bevacizumab / $X
$X
NP / CapeOx - Bevacizumab /
  • TREE-2 Study found that CapeOx with bevacizumab had improved OS over CapeOx alone (24.6 months versus 17.2 months) and equivalent safety.
/ $X
$X
NP / Cetuximab alone /
  • KRAS WT only
  • Failed previous metastatic treatment. For patients who cannot tolerate irinotecan or oxaliplatin
/ $X
$X
NP / Panitumumab alone /
  • KRAS WT only
  • Failed previous metastatic treatment. For patients who cannot tolerate irinotecan or oxaliplatin
/ $X
$X

07-2014