1. Is there a role for adjuvant oxaliplatin in rectal cancer? - YES! -
Axel Grothey
Professor of Oncology
Mayo Clinic, Rochester

2. Does adjuvant chemotherapy work at all in rectal cancer?

3. Bosset et al., Lancet Oncol 2014 EORTC 22921
252
253
253
253

4. Conclusions EORTC 22921
“Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy (with or without chemotherapy) does not affect disease-free survival or overall survival.”

5. DFS EORTC 22921
Bosset et al., Lancet Oncol 2014

6. Critique EORTC 22921 1011 pts accrued from 1993-2003
2x2 design with 250 pts per arm
T3/T4 tumors, pretreatment LN staging not documented
yN+ between 21-37%
4 cycles of a dose-reduced, abbreviated Mayo Clinic bolus 5-FU/LV regimen
Less than 43% of pts received planned dose

7. Stage II&III Rectal Cancer Treated with Pre-op Fluoropyrimidines + RT +/- Oxaliplatin
Study
# Pts
ChemoRT Regimen
ypCR Rate
(%)
ACCORD 12
(JCO 2010)
291
Cape+RT 14
293
Cape + Oxali
50mg/m2 wkly+RT
19 (p=0.09)
STAR-01
(JCO 2011)
379
FU CI+RT 16
368
FU CI + Oxali
60mg/m2 wkly+RT
16 (p=NS)
NSABP R-04
(JCO 2014)
636
FU/Cape+RT 18
640
FU/Cape + Oxali
20 (p=0.42)
PETACC-6
(ASCO 2014)
547 12
14 (p=0.27)
CAO/ARO/AIO-04
615 13
596
17 (p=0.04)*
* Unplanned exploratory analysis

8. ADORE study schema R Adjuvant FOLFOX Adjuvant 5-FU/LV
Every 2 weeks x 8 cycles
n = 149
Preop FP with radiation 
TME
ypStage II (ypT3-4N0)
ypStage III (ypTanyN1-2) R
Adjuvant 5-FU/LV
Days 1-5 q 4 weeks x 4 cycles
n = 146
1:1
Primary Endpoint: 3-year DFS
Secondary Endpoints: AEs
Patterns of failure OS
QOL
Kim et al., ASCO 2014

9. Kim et al., ASCO 2014

10. Kim et al., ASCO 2014

11. Kim et al., ASCO 2014

12. DFS – Adjuvant Rectal Ca Trials
STUDY
REGIMEN
# pts
% LN+
3 yr DFS HR
ADORE
“Mayo”
321
62 (yp N+) 63
mFOLFOX6 72
0.63 p=0.03
AIO-04
5-FU
1265
72 (clinical) 71
FOLFOX6 76
0.79 p=0.03
PETACC-6
Cap
1094
71 (clinical) 75
CAPOX 74
1.04 p=0.78
NSABP C-07
2407
FLOX
0.80 p=0.003
MOSAIC
2246 60 73
FOLFOX4 78
0.77 p=0.002
Rectal
Colon
Rectal cancer trials from ASCO 2014

13. Conclusions from the rectal cancer studies
Adjuvant therapy in rectal cancer should be guided by same principles as in colon cancer
Adjuvant oxaliplatin-based therapy is superior to FP alone in stage III (assessed before neo-adjuvant therapy!)
Supported by similarities in biology between colon and rectal cancer in TCGA
Oxaliplatin does not provide benefit as radiation sensitizer in the neoadjuvant setting
ypCR rates not increased in 4/5 studies
 Validates current clinical practice

14. TCGA Consortium, Nature 2012

15. TCGA Consortium, Nature 2012

16. NCCN