Post G.I. ASCO Update: Colorectal Cancer
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Transcript of Post G.I. ASCO Update: Colorectal Cancer
Post G.I. ASCO Update:Colorectal Cancer
Ronald Burkes, M.D.
Disclosure of Potential Conflicts of Interest
Dr. Ronald Burkes
Amgen Inc., Eli Lilly and Company, Hoffmann-La Roche, AstraZeneca, Sanofi-Aventis
Advisory board:
Honoraria: Amgen Inc., Eli Lilly and Company, Hoffmann-La Roche, AstraZeneca, Sanofi-Aventis
Speaker: Amgen Inc., Eli Lilly and Company, Hoffmann-La Roche, AstraZeneca
Objective(s) Review what was new and interesting from G.I.
ASCO, 2012 Put these results in perspective Studies to be reviewed:
181 study – FOLFIRI +/- Panitumumab as 2nd-line treatment of mCRC
NCIC CO.20 study – Cetuximab +/-Brivanib in KRAS WT mCRC (3rd-line)
CORRECT trial – BSC +/- Regorafenib in mCRC (4th-line)
XELOXA trial (N016968) – role of adjuvant XELOX for stage III CRC
ACCORD 12 trial – Capox in rectal cancerAssessment of the prognostic and predictive value of
mutant KRAS codons 12 & 13
FOLFIRI +/- Panitumumab as 2nd-line Therapy of mCRC: 181 study
Sobrero GI ASCO (#387), 2012
FOLFIRI + P303
FOLFIRI284
HR/p-value
RR 36% 9.8%PFS (mos) 6.7 4.9 .82/.023OS (mos) 14.5 12.5 .92/.37
Post Rx EGFR MoAb
12% 34%
OS (mos) by ST (2-4 vs 0-1)
16.4 vs 8.4 12.7 .5 vs 1.48
Comments: 181 Final analysis is consistent with the primary analysis There is an improvement in PFS and RR but not OS Not likely to be used as a 2nd-line option since no OS
but may be appropriate for some pts when response is necessary (? still potentially resectable)
Rash/efficacy interaction seems to be important, but not well understood
The inability to mount a skin reaction to an anti- EGFR antibody seems to be associated with a shorter survival → what should we do with patients who don’t develop a rash (should they stop the anti-EGFR MoAb) ?
Brivanib – anti-VEGFR2 inhibitor and also targets fibroblast growth receptors
Cetuximab +/- Brivanib in Refractory KRAS WT mCRC: NCIC CO.20
Siu GI ASCO (#386), 2012
Cetux + Ber376
Cetux + Pl374
HR/p-value
OS (mos) 8.8 8.1 .88/.12PFS (mos) 5 3.4 .72/<.0001
RR 13.6% 7.2% .004DI cetux 57% 83%
AEs (gr3/4) 78% 53%D/C Cetux/Br 8%/22% 4%/3%
Comments: CO.20 PFS and RR benefit but no OS benefit
(primary endpoint!) → no significant x-over Toxicity of the combination may have
confounded efficacy → DI; D/C Rx 20 AEs Potential biological antagonism → PACCE and
CAIRO-2 Unlikely to gain regulatory approval and/or use
in combination with cetuximab Phase III HCC monotherapy trials are ongoing
NB: no PS 2 patients on study
Even
t-f
ree
Prob
abili
ty
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Weeks from Randomization0 8 16 24 32 40 48 56
Hazard ratio=0.54 (95% CI: 0.44, 0.66)
Stratified log-rank testp < 0.000000001
ProgressionProgression--Free SurvivalFree Survival
Panitumumab
BSC
Patients at risk:PanitumumabBSC
231 118 49 31 13 5 1232 75 17 7 3 1 1
Primary Analysis, All Randomized Analysis Set, Central Radiology
BSC +/- Regorafinib in Refractory mCRC: CORRECT Trial (no PS2, no x-over)
Grothey GI ASCO (#385), 2012
Regorafinib505
BSC255
HR/p-value
KRAS mut 54.1% 61.6%
MST (mos) 6.4 5 .77/.0052
PFS (mos) 1.9 1.7 .49/<.00001
RR/DCR 1%/44.8% .4%/15.3% p<.000001
Toxicity H/F, ↑BP, Diarrhea
D/C 20 AEs 8.2% 1%
Comments: CORRECT• OS and PFS benefit
– Statistically significant– Clinically meaningful– Toxicity profile not insiginificant (H/F,
diarrhea, fatigue, ↑BP) but acceptable– Lack of x-over helped achieve endpoints
• Clinical impact– Likely to become an available standard for
refractory mCRC – when??? (unmet need)– Role in PS 2 patients is unknown– Role of continuous dosing is unknown
X-ACT vs XELOXA
Cape Mayo HR/p Bolus Xelox HR/p
N 1004 983 942 944DFS 60.8% 56.7% .88/<.0001(.068) 59.8% 66.1% .8/.0038
OS 71.4% 68.4% .86/<.0001(.06) 70% 75% .83/.038
X-ACT XELOXA
Twelves GI ASCO (#274), 2008
Twelves GI ASCO (#274), 2008
Comments: XELOXA XELOX improves DFS and OS compared to bolus
5-FU in patients with stage III colon cancer (median follow-up of 7 years)
Benefit is less in patients > 70 years XELOX should be considered a treatment option
in the adjuvant therapy of stage III colon cancerq3weeks less infusion time (impact on chemo unit) less need for central lines it is not for everyone – keep a close watch for toxicity
Capecitabine + RT(45) vs Capox + RT (50) in Rectal Cancer: ACCORD 12 Trial
Gerard GI ASCO (#389), 2012
Cape 45299
Capox 50299
DFS (3 yrs) 68.3% 73.7%
OS (3 yrs) 87.6% 88.3%
pCR 13.9% 19.2%
Local recurrence 6.1% 4.7%
Systemic recurrence 25% 21%
Diarrhea gr ¾ 11% 25%
Comments: ACCORD 12 This study introduced 3 changes to the
approach to the pre-operative therapy of rectal cancer
Oxaliplatin increases toxicity (diarrhea) without any significant impact on ypCR (not a radiosensitizer), local or systemic recurrences, DFS and OS
50Gy/5 weeks compatible with surgery and also increased the CRM negative rate
Capecitabine has the same activity as 5-FU
Comments: KRAS Mutation Analysis in mCRCPeeters GI ASCO (#383), 2012
Patients with mCRC that harbor most of the common codon 12 and 13 mutant KRAS alleles are unlikely to benefit from panitumumab therapy
Currently only mCRC patients with WT KRAS tumors should be treated with anti-EGFR MoAbs