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Adjuvant Oxaliplatin for Stage 3 Colon Cancer Kanwal Pratap Singh Raghav
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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
QUESTION HOW CAN WE IDENTIFY STAGE III COLON CANCER
PATIENTS WHO DO NOT BENEFIT FROM OXALIPLATIN BASED ADJUVANT THERAPY?
SUBJECT: CLINICAL MARKERS
STAGE III: CURRENT GUIDELINES
NCCN guidelines (nccn.org); Edge et al. AJCC Cancer Staging Manual 2010.
* 5-yr Survival Rate (%) [1998-2000]
*
STAGE III: CURRENT GUIDELINES
Node-Positive
NCCN guidelines (nccn.org); Edge et al. AJCC Cancer Staging Manual 2010.
* 5-yr Survival Rate (%) [1998-2000]
*
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]
*
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]
*
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
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
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
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
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
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
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
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)
OXALIPLATIN BENEFIT: CLINICAL PREDICTORS
MO
SAIC
Stu
dy
NSABP C-07 Study
Yothers et al. JCO 2011; Andre et al. JCO 2009
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
STAGE III CLINICAL SCENARIOS: A HETEROGENOUS DISEASE
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.
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!
DISCUSSION
