Transcript ASCO_2012_files/Berlin Translational GI Cancers ASCO

Jointly sponsored by Postgraduate Institute for
Medicine and Clinical Care Options, LLC
In partnership with Translational
Research in Oncology
Translational Research 2012:
Using Leading-Edge Science to Make
the Correct Treatment Choice Today
and Tomorrow
Sunday, June 3, 2012
6:30 PM – 8:30 PM
Hyatt Regency Chicago
Chicago, Illinois
This program is supported by educational grants from
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Current and Future Directions in the
Treatment of GI Cancers: Optimizing
Treatment by Genetic Features of Disease
Jordan D. Berlin, MD
Associate Professor of Medicine
Vanderbilt University
Clinical Director, GI Oncology
The Vanderbilt-Ingram Cancer Center
Nashville, Tennessee
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Translational Research 2012
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Outline
 EGFR-targeted antibodies in CRC
– Rationale for and data supporting KRAS mutation testing
 Biomarkers for future treatment algorithms
– Impact of BRAF mutations on EGFR-targeted therapy
– Other potential biomarkers
– CTC levels
 Role of HER2 in gastric cancer
– Rationale for and data supporting use of HER2-targeted therapies
 Biomarkers for future treatment algorithms
– Other potential biomarkers
EGFR-Targeted Antibodies
in Colorectal Cancer
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EGFR-Targeted Antibodies in CRC
 EGFR-targeted antibodies approved in CRC
– Cetuximab
– Panitumumab
 EGFR expression status insufficient for discerning which patients
derive most benefit
 KRAS: signaling molecule downstream of EGFR
– Mutated KRAS becomes constitutively active, negating effect of
EGFR inhibition[1]
– ~40% of CRCs have mutated KRAS genotype[1]
– Mutated KRAS associated with poor response to EGFR-targeted
agents[2]
1. Lièvre A, et al. Oncogene. 2010;29:3033-3043. 2. Dahabreh IJ, et al. Ann Intern Med. 2011;154:37-49.
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KRAS Testing: What Are the
Recommendations?
 NCCN guidelines[1]
– Strongly recommend KRAS testing in all patients with mCRC at
the time of diagnosis of metastatic disease
– Testing should be performed in a CLIA-certified lab
– Testing can be performed on either primary or metastatic tissue
 ASCO Provisional Clinical Opinion[2]
– All patients with mCRC who are candidates for anti-EGFR
antibody therapy should have their tumor tested for KRAS
mutations in a CLIA-accredited laboratory
 In both cases, anti-EGFR agents (cetuximab and panitumumab)
are recommended for wild-type KRAS patients only[1,2]
1. NCCN. Clinical practice guidelines in oncology: colon cancer. 2012.
2. Allegra CJ, et al. J Clin Oncol. 2009;27:2091-2096.
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Studies Evaluating Addition of EGFRTargeted Antibody to Chemotherapy
 Benefit in KRAS wild-type CRC patients only
– CRYSTAL: cetuximab plus FOLFIRI[1]
– OPUS: cetuximab plus FOLFOX-4[2]
– PRIME: panitumumab plus FOLFOX-4[3]
 No benefit in either KRAS wild-type or mutated CRC
patients
– COIN: cetuximab plus oxaliplatin/fluoropyrimidine[4]
1. Van Cutsem E, et al. J Clin Oncol. 2011;29:2011-2019. 2. Bokemeyer C, et al. Ann Oncol. 2011;22:15351546. 3. Douillard JY, et al. J Clin Oncol. 2010;28:4697-4705. 4. Maughan TS, et al. Lancet.
2011;377:2103-2114.
Expert Insight Into the First-line Treatment of Metastatic Colorectal Cancer
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CRYSTAL: KRAS Status in Response to
Cetuximab
 Randomized, multicenter phase III trial[1]
– Significant improvement in PFS with addition of cetuximab to
FOLFIRI vs FOLFIRI alone for first-line mCRC treatment
 Updated survival analysis of
CRYSTAL[2]
– Included only subset
of KRAS-evaluable
patients (n = 1063)
Stratified by geographic
region, ECOG PS
EGFR-positive patients
with previously
untreated mCRC
(N = 1218)
*FOLFIRI: irinotecan 180 mg/m2, folinic acid 400 mg/m2, 5-FU 400 mg/m2 bolus,
5-FU infusion 2.4 g/m2 over 46 hrs.
†Cetuximab: 400 mg/m2 on Day 1, then 250 mg/m2/wk.
1. Van Cutsem E, et al. N Engl J Med. 2009;360:1408-1417.
2. Van Cutsem E, et al. J Clin Oncol. 2011;29:2011-2019.
FOLFIRI* 2-wk cycle
(n = 609)
FOLFIRI* 2-wk cycle +
Cetuximab†
(n = 609)
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CRYSTAL: Updated Survival Analysis
Efficacy Results
 Significant interactions between KRAS status and treatment
outcome observed with PFS, OS, and ORR efficacy outcomes
– Survival and response benefits with addition of cetuximab only
achieved in KRAS wild-type patients
Cetuximab +
FOLFIRI
FOLFIRI
Hazard Ratio
P value
Wild-type KRAS
 Median PFS, mos
 Median OS, mos
 ORR, %
9.9
23.5
57.3
8.4
20.0
39.7
0.696
0.796
2.069*
.0012
.0093
< .001
Mutated KRAS
 Median PFS
 Median OS
 ORR, %
7.4
16.7
31.3
7.7
16.2
36.1
1.171
1.035
0.822*
.26
.75
.35
Outcome
*Odds ratio
Van Cutsem E, et al. J Clin Oncol. 2011;29:2011-2019.
Expert Insight Into the First-line Treatment of Metastatic Colorectal Cancer
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OPUS: KRAS Status in Response to
Cetuximab
 Randomized, open-label, multicenter phase II trial[1]
– Significant improvement in ORR with addition of cetuximab
to FOLFOX-4 vs FOLFOX-4 alone for first-line mCRC
treatment
 Biomarker analysis of
OPUS[2]
– Included only subset
of KRAS-evaluable
patients (n = 315)
EGFR-positive patients
with previously
untreated mCRC
(N = 344)
*FOLFOX-4: oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 bolus,
5-FU infusion 600mg/m2 over 22 hrs.
†Cetuximab: 400 mg/m2 on Day 1, then 250 mg/m2/wk.
1. Bokemeyer C, et al. J Clin Oncol. 2009;27:663-671.
2. Bokemeyer C, et al. Ann Oncol. 2011;22:1535-1546.
FOLFOX-4*
(n = 168)
FOLFOX-4* +
Cetuximab†
(n = 169)
Expert Insight Into the First-line Treatment of Metastatic Colorectal Cancer
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OPUS: Biomarker Analysis OS Results
Bokemeyer C, et al. Ann Oncol. 2011;22:1535-1546.
Expert Insight Into the First-line Treatment of Metastatic Colorectal Cancer
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Meta-Analysis: KRAS Status in Response
to Cetuximab
 Pooled efficacy analysis of CRYSTAL and OPUS studies
– CRYSTAL: FOLFIRI + cetuximab vs FOLFIRI alone[2]
– OPUS: FOLFOX + cetuximab vs FOLFOX alone[3]
 90% of samples were subjected to KRAS genotype testing
– HRs for benefit of addition of cetuximab highly statistically
significant in patients with wild-type KRAS
– PFS
– HR: 0.66 (P < .0001)
– OS
– HR: 0.81 (P = .0062)
Bokemeyer C, et al. ASCO 2010. Abstract 3506.
Expert Insight Into the First-line Treatment of Metastatic Colorectal Cancer
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PRIME: KRAS Status in Response to
Panitumumab
 Randomized, global, open-label, phase III trial
Stratified by ECOG PS (0-1 vs 2)
and geographic region (Western
Europe, Canada, and Australia vs all
other locations)
Patients with
previously
untreated mCRC
Panitumumab 6.0 mg/kg q2w +
FOLFOX4 q2w
(n = 593)
(N = 1183)
Douillard JY, et al. J Clin Oncol. 2010;28:4697-4705.
FOLFOX4 q2w
(n = 590)
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PRIME: Efficacy Results


Wild-type KRAS patients
Mutated KRAS patients
– PFS significantly improved with
FOLFOX4 + panitumumab
– Worse PFS outcome with
panitumumab addition
– HR: 0.80,; 95% CI: 0.67-0.96;
P = .01
– HR: 1.27; 95% CI: 1.04-1.55;
P = .02
Panitumumab +
FOLFOX4
FOLFOX4
P value
Wild-type KRAS
 Median PFS
 Median OS
10.0
23.9
8.6
19.7
.01
.17
Mutated KRAS
 Median PFS
 Median OS
7.4
15.5
9.2
19.2
.02
.15
Outcome, mos
Douillard JY, et al. J Clin Oncol. 2010;28:4697-4705.
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MRC COIN: KRAS Status in Response to
Cetuximab
 Randomized, open-label trial
– Largest to assess addition of cetuximab to chemotherapy in
first-line treatment of mCRC
– Prospective analysis of efficacy in relation to KRAS mutation
status
Patients
with previously
untreated mCRC
irrespective of EGFR
status
(N = 344)
OxFP*
(n = 815)
OxFP* +
Cetuximab†
(n = 815)
3rd treatment arm randomized patients
to interittent OxFP (n = 815)
Maughan TS, et al. Lancet. 2011;377:2103-2114.
*OxFP: oxaliplatin 130 mg/m2 plus
capecitabine 850 mg/m2 twice daily
for 2 weeks, or oxaliplatin 85 mg/m2
plus leucovorin 175 or 350 mg and
5-FU 400 mg/m2 bolus then
5-FU infusion 2400 mg/m2 over 46
hrs.
†Cetuximab: 400 mg/m 2 on Day 1,
then 250 mg/m2/wk.
Expert Insight Into the First-line Treatment of Metastatic Colorectal Cancer
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MRC COIN: Survival Efficacy Results
 No improvement in either OS or PFS with addition of
cetuximab to chemotherapy in KRAS wild-type patients
KRAS
wild-type
OxFP
OxFP + Cetuximab
Maughan TS, et al. Lancet. 2011;377:2103-2114.
KRAS
mutated
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KRAS: Not all Mutations are Equal
 Mutation pattern[1]
– 79% of CRC tumors have mutations in codon 12
– 17.6% of CRC tumors have mutations in codon 13
 Anecdotal reports suggest < 10% of KRAS-mutated CRC patients can
respond to anti-EGFR therapy[2,3]
– Codon 13 mutations overrepresented in these tumors
 Codon 13 mutations show weaker transforming activity in vitro[4]
 KRAS G13D mutation associated with longer OS and PFS vs other
KRAS mutations[1]
1. De Roock W, et al. JAMA. 2010;304:1812-1820. 2. Benvenuti S, et al. Cancer Res. 2007;67:2643-2648.
3. Moroni M, et al. Lancet Oncol. 2005;6:279-286. 4. Guerrero S, et al. Cancer Res. 2000;60:6750-6756.
A Vision of Tomorrow’s
Treatment Algorithm:
Colorectal Cancer
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Impact of BRAF Mutations on Anti-EGFR
Therapy
 5% to 9% of CRC tumors have specific BRAF V600E mutation[1,2]
– Results in constitutive activation of BRAF protein
– Typically do not occur in tumors with KRAS exon 2 mutations[2]
 Outcomes with BRAF V600E mutation
– Non-first-line setting: BRAF V600E mutation associated with
resistance to EGFR-targeted agents[3-5]
– First-line setting: BRAF V600E mutation associated with poorer
prognosis, but some patients may still benefit from addition of
cetuximab to chemotherapy[6-7]
1. Van Cutsem E, et al. ASCO 2010. Abstract 3570. 2. Tol J, et al. NEJM. 2009;361:98-99. 3. Di
Nicolantonio F, et al. J Clin Oncol. 2008;26:5705-5712. 4. Laurent-Puig P, et al. J Clin Oncol.
2009;27:5924-5930. 5. Loupakis F, et al. Br J Cancer. 2009;101:715-721. 6. Van Cutsem E, et al. J Clin
Oncol. 2011;29:2011-2019. 7. Bokemeyer C, et al. ASCO 2010. Abstract 3506.
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BRAF Mutations in First-Line Setting
 CRYSTAL and OPUS meta-analysis
– Patients with wild-type KRAS/mutated BRAF
– Worse outcomes vs wild-type KRAS/wild-type BRAF
– Still experienced non-significant improvements (small N)
Outcome
Wild-type KRAS/
Mutated BRAF
Wild-type KRAS/
Wild-type BRAF
Cetuximab
+ CT
CT Only
P Value
Cetuximab
+ CT
CT Only
P Value
Median PFS,
mos
7.1
3.7
.267
10.9
7.7
< .001
Median OS,
mos
14.1
9.9
.079
24.8
21.1
.041
Median ORR, %
21.9
13.2
.4606
60.7
40.9
< .0001
Bokemeyer C, et al. ASCO 2010. Abstract 3506.
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Other Potential Biomarkers in CRC

PI3K: 39%[1]
– Associated with significantly
decreased PFS in patients treated
with FOLFIRI plus cetuximab[1]


– Associated with poor prognosis[5]

EGFR ligands
– Surrogate markers for EGFR
inhibition with cetuximab[3]
Defective mismatch repair: 15%[6]
– Improved prognosis and stagedependent survival[7]
NRAS: 2%[2]
– Prognostic/predictive value
unclear[2]

DNA hypermethylation: 30%[4]
– Predictive for lack of efficacy of 5FU-based adjuvant therapy[8]

VEGF receptors and ligand
– VEGF expression may be
associated with poorer prognosis[9]
1. Linot B, et al. ASCO 2010. Abstract 365. 2. Irahara N, et al. Diagn Mol Pathol. 2010;19:157-163. 3. Cremolini C, et al.
ASCO 2010. Abstract 99. 4. Kulendran M, et al. Cancers. 2011;3:1622-1638. 5. Barault L, et al. Cancer Res. 2008;68:85418546. 6. Kerr DJ. J Clin Oncol. 2010;28:3210-3212. 7. Popat S, et al. J Clin Oncol. 2005;23:609-618. 8. Sargent D, et al. J
Clin Oncol. 2010;28:3219-3227. 9. Bendardaf R, et al. Anticancer Res. 2008;28:3865-3870.
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CTC Levels
 mCRC patients treated with chemotherapy plus targeted agents in
CAIRO2 phase III trial (N = 467)[1]
– Higher CTC count at baseline and during treatment associated
with lower survival vs lower CTC count
– PFS HR: 1.5
– OS HR: 2.2
 mCRC patients (N = 430)[2]
– Higher CTC count at baseline and during treatment associated
with lower survival vs lower CTC count
– PFS: 4.4 vs 7.8 months, P = .004
– OS: 9.4 vs 20.6 months, P < .0001
1. Tol J, et al. Ann Oncol. 2010;21:1006-1012. 2. Cohen SJ, et al. Ann Oncol. 2009;20:1223-1229.
Role of HER2 in Gastric Cancer
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Rationale for Targeting HER2 in Gastric
Cancer
 10% to 25% tumors overexpress HER21
 HER2 overexpression associated with poor prognosis2
– Poor survival
– Serosal invasion
– Lymph node metastases
– Disease stage
– Distant metastases
1. Yano T, et al. Oncol Rep. 2006;15:65-71.
2. Jorgensen JT, et al. J Cancer. 2012;3:137-144.
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Chemotherapy Treatment of HER2Positive Gastric Cancer Patients
 Patients with initially metastatic or recurrent gastric
cancer, treated with first-line mFOLFOX-6
Outcome, mos
HER2-positive
HER2-negative
P value
Median TTP
4.3
5.9
0.177
Median OS
7.5
10.8
0.068
 TTP particularly worse in HER2-positive patients without
diffuse-type histology
Kim JW, et al. Anticancer Res. 2012;32:1547-1553.
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Challenges Determining HER2 Status in
Gastric Cancer
 HER2 testing in gastric cancer differs from breast cancer
– More frequent HER2 heterogeneity (focal staining)
– Incomplete membrane staining
 Testing protocol
– Initial testing with IHC
– Retest IHC 2+ samples with FISH
Rüschoff J, et al. Mod Pathol. 2012;25:637-650.
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HER2 Positivity: IHC
Score
Surgical Specimen
Staining Pattern
Biopsy Specimen Staining
Pattern
HER2 Overexpr.
Assessment
0
No reactivity or
membranous
reactivity in < 10% of
tumor cells
No reactivity or no
membranous reactivity
in any tumor cell
Negative
1+
Faint or barely perceptible
membranous reactivity in
≥ 10% of tumor cells; cells
are reactive only in part of
their membrane
Tumor cell cluster with faint or
barely perceptible membranous
reactivity irrespective of % of
tumor cells stained
Negative
2+
Weak to moderate
complete, basolateral or
lateral membranous
reactivity in ≥ 10% of
tumor cells
Tumor cell cluster with weak to
moderate complete, basolateral
or lateral membranous reactivity
irrespective of % of tumor cells
stained
Equivocal
3+
Strong complete,
basolateral or lateral
membranous reactivity in
≥ 10% of tumor cells
Tumor cell cluster with strong
complete, basolateral or lateral
membranous reactivity
irrespective of % of tumor cells
stained
Positive
Bang YJ, et al. Lancet. 2010;376:687-697.
Bang YJ, et al. ASCO 2009. Abstract 4556.
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Trastuzumab + Chemotherapy in
Advanced HER2+ Gastric Cancer: ToGA
 Rationale: a subpopulation of gastric cancers overexpress HER2
Stratified by ECOG PS,
advanced vs metastatic, gastric vs GEJ,
measurable disease, capecitabine vs 5-FU
Patients with
advanced
gastric cancer
screened for
HER2 status
(N = 3803)
Patients with
HER2+
advanced
gastric cancer
(n = 810; 22% of
successful
screenings)
R
(n = 584)
5-FU or Capecitabine* +
Cisplatin 80 mg/m2 q3w x 6 +
Trastuzumab 6 mg/kg q3w until PD
(8 mg/kg loading dose)
(n = 294)
5-FU or Capecitabine* +
Cisplatin 80 mg/m2 q3w x 6
(n = 290)
 Primary endpoint: OS
*Selected at investigator’s discretion: 5-FU 800 mg/m2/day infusional on Days 1-5 q3w x 6;
capecitabine 1000 mg/m2 BID on Days 1-14 q3w x 6.
Bang YJ, et al. Lancet. 2010;376:687-697.
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ToGA: HER2 Positivity Worldwide
Asian/Pacific
35
Europe
South/Middle
America
Other
Patients, %
30
25
20
15
10
5
0
Bang YJ, et al. ASCO 2009. Abstract 4556.
HER2 positivity in ToGA: 22.1%
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ToGA: HER2 Positivity Histological Type
Histological type
Localization
Subtype
HER2 Positivity (%)
P Value
Intestinal
Diffuse
Mixed
32.2
6.1
20.4
< .001
GEJ
Gastric
33.2
20.9
< .002
Histological subtype and tumor sublocalization are important factors
for HER2 expression/amplification in gastric cancer
Bang YJ, et al. ASCO 2009. Abstract 4556.
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ToGA: HER2 Positivity GEJ vs Gastric
Cancer
100
Gastric cancer
GEJ cancer
Samples (%)
80
60
40
20
0
N = 2759; *P < .001
HER2 positive, %
Bang YJ, et al. ASCO 2009. Abstract 4556.
Gastric Cancer
GEJ Cancer
Total
20.9
33.2*
21.3
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Survival Probability
ToGA: Primary Endpoint OS
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Median
Events OS
HR
FC + T
FC
11.1
0
2
4
6
167
182
13.8
11.1
95% CI P Value
0.74 0.60-0.91
13.8
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Mos
Pts at Risk, n
294 277 246 209 173 147 113 90
290 266 223 185 143 117 90 64
Bang YJ, et al. Lancet. 2010;376:687-697.
71
47
56
32
43
24
30
16
21
14
13
7
12
6
6
5
4
0
1
0
0
0
.0046
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ToGA: Efficacy Outcomes
Outcome
Chemotherapy
+ Trastuzumab
(n = 294)
Chemotherapy
Alone
(n = 290)
HR (95% CI)
P Value
Median OS, mos
13.8
11.1
0.74 (0.60-0.91)
.0046
Median PFS, mos
6.7
5.5
0.71 (0.59-0.85)
.0002
ORR, %
47
35
-
.0017

CR
5
2
-
.0599

PR
42
32
-
.0145
 Preplanned subgroup analysis indicated improved OS benefit with
increasing HER2 expression by IHC
 Exploratory analysis of IHC 2+/FISH+ and IHC 3+ cohort
demonstrated a 4-mo increase in OS with trastuzumab
– HR: 0.65 (95% CI: 0.51-0.83)
Bang YJ, et al. Lancet. 2010;376:687-697.
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ToGA: OS by HER2 Status
HER2 Status Subgroup
All patients (N = 584)
Median OS, Mos
(CT + T vs CT Alone)
HR* (95% CI)
13.8 vs 11.1
0.74 (0.60-0.91)
Preplanned analysis

IHC 0/FISH+ (n = 61)
10.6 vs 7.2
0.92 (0.48-1.76)

IHC 1+/FISH+ (n = 70)
8.7 vs 10.2
1.24 (0.70-2.20)

IHC 2+/FISH+ (n = 159)
12.3 vs 10.8
0.75 (0.51-1.11)

IHC 3+/FISH+ (n = 256)
17.9 vs 12.3
0.58 (0.41-0.81)

IHC3+/FISH- (n = 15)
17.5 vs 17.7
0.83 (0.20-3.38)
Exploratory analysis

IHC 0 or 1+/FISH+ (n = 131)
10.0 vs 8.7
1.07 (0.70-1.62)

IHC 2+/FISH+ or IHC 3+ (n = 446)
16.0 vs 11.8
0.65 (0.51-0.83)
*HR < 1 favors chemotherapy + trastuzumab; HR > 1 favors chemotherapy alone.
Bang YJ, et al. Lancet. 2010;376:687-697.
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Survival Probability
ToGA: OS in IHC 2+/FISH+ or IHC 3+
(Exploratory Analysis)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Median
Events OS
HR
FC + T
FC
11.8
0
2
4
6
120
136
16.0
11.8
95% CI
0.65 0.51-0.83
16.0
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Mos
Pts at Risk, n
228 218 196 170 142 122 100 84
218 198 170 141 112 96 75 53
Bang YJ, et al. Lancet. 2010;376:687-697.
65
39
51
28
39
20
28
13
20
11
12
4
11
3
5
3
4
0
1
0
0
0
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ToGA: Select Toxicities
Adverse Event, %
Chemotherapy + Trastuzumab
(n = 294)
Chemotherapy Alone
(n = 290)
Grade 3/4 hematologic events

Neutropenia
27
30

Anemia
12
10
Grade 3/4 nonhematologic
events

Diarrhea
9
4

Nausea
7
7
Cardiac events
6
6

1
3
5
1
Grade 3/4
LVEF reduction of ≥ 10% to
absolute value < 50%*
*Chemotherapy plus trastuzumab: n = 237; chemotherapy alone: n = 187.
Bang YJ, et al. Lancet. 2010;376:687-697.
A Vision of Tomorrow’s
Treatment Algorithm:
Gastric Cancer
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Other Potential Biomarkers in Gastric
Cancer

MicroRNAs
– Unique microRNAs associated with distinct prognostic and predictive values [1,2]
– 7-microRNA signature independent predictor of OS and RFS[3]

DNA methylation
– Prognostic/predictive value[4]

CEA
– Elevated levels correspond with worse prognosis and survival[5]

Cyclin D1
– Elevated levels correspond with worse prognosis[6]
1. Ueda T, et al. Lancet Oncol. 2010;11:136-146. 2. Li X, et al. Gut. 2010;59:579-585. 3. Brenner B, et al.
World J Gastroenterol. 2011;17:3976-3985. 4. Sapari NS, et al. PLoS One. 2012;7:e36275. 5. Mihmanli M,
et al. Hepatogastroenterology. 2004;51:1544-1547. 6. Gao P, et al. World J Gastroenterol. 2004;10:29362939.
Translational Research 2012
clinicaloptions.com/oncology
Summary

KRAS mutation status critical determinant of benefit with EGFR-targeted
antibody therapy
– BRAF mutations potentially predictive of reduced benefit in non-first-line
setting

Future biomarkers in CRC
– PI3K, NRAS, EGFR ligand, DNA hypermethylation, mismatch repair,
VEGF, CTC levels

HER2 expression confers worse prognosis in gastric cancer
– HER2 expression challenging to assess and should be performed only by
experienced pathologists

Future biomarkers in gastric cancer
– MicroRNAs, DNA methylation, CEA, cyclin D1
Go Online for More CCO
Coverage of GI Cancers!
Capsule Summaries of all the key data, plus Expert Analysis panel
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Expert Recap (slides and audio) plus
downloadable PowerPoint slides
clinicaloptions.com/oncology