Download - Stage 3 colon cancer
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STAGE III COLON CANCER&
ADJUVANT OXALIPLATINAnnual Updates on Breakthroughs in Hematology & Oncology (AUBHO) 2014
Kanwal Pratap Singh Raghav, MDThe University of Texas M.D. Anderson Cancer Center, Houston, TX
30th August 2014
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QUESTION HOW CAN WE IDENTIFY STAGE III COLON CANCER
PATIENTS WHO DO NOT BENEFIT FROM OXALIPLATIN BASED ADJUVANT THERAPY?
SUBJECT: CLINICAL MARKERS
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STAGE III: CURRENT GUIDELINES
NCCN guidelines (nccn.org); Edge et al. AJCC Cancer Staging Manual 2010.
* 5-yr Survival Rate (%) [1998-2000]
*
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STAGE III: CURRENT GUIDELINES
Node-Positive
NCCN guidelines (nccn.org); Edge et al. AJCC Cancer Staging Manual 2010.
* 5-yr Survival Rate (%) [1998-2000]
*
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STAGE III: CURRENT GUIDELINES
Node-Positive
N1 (1-3) T1 T2 T3 T4a T4bN2a (4-6) T1 T2 T3 T4a T4bN2b (≥7) T1 T2 T3 T4a T4b
IIIA 73IIIB 46IIIC 28
NCCN guidelines (nccn.org); Edge et al. AJCC Cancer Staging Manual 2010.
* 5-yr Survival Rate (%) [1998-2000]
*
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STAGE III: CURRENT GUIDELINES
Node-Positive
N1 (1-3) T1 T2 T3 T4a T4bN2a (4-6) T1 T2 T3 T4a T4bN2b (≥7) T1 T2 T3 T4a T4b
IIIA 73IIIB 46IIIC 28
Oxaliplatin: Category 1
NCCN guidelines (nccn.org); Edge et al. AJCC Cancer Staging Manual 2010.
* 5-yr Survival Rate (%) [1998-2000]
*
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STAGE III: ADJUVANT 5FU ACTIVITY
NCCTG Trial (1990) (N = 929)↓ Recurrence rate 40%↓ Death rate 33%
Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
Colon CancerDukes Stage C
Surgery
Observation
Levamisole
5FU + Levamisole
ADJCCA-01 Trial (2001) N = 680: 5FU/Leucovorin v. 5FU/LevamisoleMedian DFS: 58 v. 49 m; P = 0.037Median OS: 63 v. 55 m; P = 0.009
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ADJUVANT ROLE OF OXALIPLATIN
Colon CancerStage III/II Surgery
LV5FU
FOLFOX
MOSAIC Trial (2004) (N = 1347)5-yr. DFS: 66.4 v. 58.9% (HR 0.78; P = 0.005)6-yr OS: 72.9 v. 68.7% (HR 0.80; P = 0.023)
}
}NSABP C-07 Trial (2007) N = 1714: 5FU/LV bolus v. FLOX5-yr. DFS: 64.4 v. 57.8% (HR 0.78; P < 0.001)5-yr OS: 76.5 v. 73.8% (HR 0.85; P = 0.052)
Yothers et al. JCO 2011; Andre et al. JCO 2009
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STAGE III: ROLE OF ADJUVANT THERAPY
Dis
ease
-Fre
e Su
rviv
al (%
)
Time (years)
Surgery alone (1990)
Yothers et al. JCO 2011; Andre et al. JCO 2009; Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
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STAGE III: ROLE OF ADJUVANT THERAPY
Dis
ease
-Fre
e Su
rviv
al (%
)
Time (years)
Surgery alone (1990)
5FU/LV (2001)
Yothers et al. JCO 2011; Andre et al. JCO 2009; Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
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STAGE III: ROLE OF ADJUVANT THERAPY
Dis
ease
-Fre
e Su
rviv
al (%
)
Time (years)
Surgery alone (1990)
FLOX (2007)
5FU/LV (2001)
Yothers et al. JCO 2011; Andre et al. JCO 2009; Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
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STAGE III: ROLE OF ADJUVANT THERAPY
Dis
ease
-Fre
e Su
rviv
al (%
)
Time (years)
Surgery alone (1990)
FLOX (2007)
5FU/LV (2001)
FOLFOX (2004)
Yothers et al. JCO 2011; Andre et al. JCO 2009; Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
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STAGE III: ROLE OF ADJUVANT THERAPY
Dis
ease
-Fre
e Su
rviv
al (%
)
Time (years)
Surgery alone (1990)
FLOX (2007)
5FU/LV (2001)
FOLFOX (2004)
5-yr. DFS ~ 66%
(22% RRR, 8% ARR)
6-yr. OS ~ 73%
(20% RRR, 4% ARR)Yothers et al. JCO 2011; Andre et al. JCO 2009; Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
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5FU RESPONSE: CLINICAL PREDICTORS
Moertel et al. Ann. Int. Med. 1995; Porschen et al. JCO 2001
NCCTG Study ADJCCA-01 Study
Factors: Nodal status, tumor invasion, tumor grade, preoperative obstruction, interval between surgery & start of chemotherapy (P < 0.05)
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OXALIPLATIN BENEFIT: CLINICAL PREDICTORS
MO
SAIC
Stu
dy
NSABP C-07 Study
Yothers et al. JCO 2011; Andre et al. JCO 2009
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AGE AS A PREDICTOR OF OXALIPLATIN BENEFIT
ACCENT Database Study
MOSAIC, NSABP C-07, XELOXA
Age: <70 yrs. & ≥70 yrs.
Benefit more with < 70 yr.
Not a significant interaction with age
McCleary et al. JCO 2013
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STAGE III CLINICAL SCENARIOS: A HETEROGENOUS DISEASE
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CONCLUSIONS
Stage III colon cancer is a heterogenous disease.
DFS & OS benefit from adjuvant 5FU & oxaliplatin.
All prognostic subgroups appear to benefit.
Age may be a clinical predictor of oxaliplatin benefit but data are conflicting.
Studies are needed to investigate “molecular biomarkers” predicting benefit from oxaliplatin chemotherapy.
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ANSWER
Question: How can we identify stage III colon cancer patients who do NOT benefit from oxaliplatin based adjuvant therapy?
Answer: We cannot clinically identify stage III colon cancer patients who do NOT benefit from oxaliplatin based adjuvant therapy, although, absolute benefit is variable & dependent upon patient/tumor characteristics. Decision to select a patient should be individualized based on risk of recurrence, absolute benefit over 5FU alone, life expectancy, comorbidities, discussion of risks-benefits and patient preference!
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DISCUSSION