Describes the most recent evidence that tumor location in metastatic colorectal cancer would affect the treatment decision.

2. Colorectal Cancer Advancements
“Does tumor location affect treatment choice?”
Mohamed Abdulla M.D.
03/11/2017

3. Member of Advisory Board, Consultant, and Speaker for:
• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag, Merck
Serono, Novartis, Pfizer, Mundipharma, MSD, Ely Lilly
Speaker Disclosures:

4. Egypt Demographics:
Gender Lower Egypt
2009 - 2011
Middle Egypt
2009
Upper Egypt
2008
Males 2.9% 2.1% 2.48%
Females 2.3% 2.3% 2.08%
Incidence Rates/100000 Population: Colon Cancer
Year 2013 2015 2020 2025 2050
Number 2862 3055 3608 4465 8585
Estimated Number of New Cases Over Time:
Ibrahim et al. Journal of Cancer Epidemiology. Volume 2014, Article ID 437971, 18 pages

5. mCRC:
The Expanding Landscape
mOAS
> 30 months
Efficacy of 1st L
“Biomarker”
Resection/Ablation of
Organ Limited Disease
More Subsequent
Treatment Options
Treatment Holidays (QoL)
Maintenance Therapy
Re-challenge Beyond
Progression
Treatment Intensification
MDT Approach
1ry Tumor Location
Tumor Immunogenicity
Vogel et al. Cancer Treatment Reviews 59 (2017) 54–60

6. CALGB/SWOG 80405: KRAS wt
1ST LINE
MET / ADVANCED
COLORECTAL
KRAS wt
Codons 12 & 13
FOLFIRI
or
FOLFOX
MD choice
Chemo + Cetuximab
OS = 29.9 mos
PFS = 10.4 mos
Chemo + Bevacizumab
OS = 29.0 mos
PFS = 10.8 mosN = 1137
PRESENTED AT THE 2014 ASCO ANNUAL MEETING DATA IS THE PROPERTY OF THE AUTHOR

7. CALGB 80405: OAS
Alan P. Venook, MD et al. JAMA June 20, 2017 Volume 317, Number 23

8. 80405: (KRAS WT) Overall Survival by Sidedness
Presented by:ASCO ANNUAL MEETING ‘16
Side
N
(Events)
Median
(95% CI)
HR
(95% CI)
p
Left 732 (550)
33.3
(31.4-35.7) 1.55
(1.32-1.82)
<
0.0001
Right 293 (242)
19.4
(16.7-23.6)

9. Right versus Left Colon:
Evidence from Literature
Outcome Right Sided Colon Left Sided Colon P
5-Y OAS 1990s 56.3% 59.7% < 0.01
5-Y OAS 2000s 67% 71% < 0.01
5-Y PFS 2010 73% 74% > 0.05
5-Y PFS 2014 88.6% 89.4% > 0.05
Median OAS 18.2 ms 29.4 ms < 0.001
Shen etal. World J Gastroenterol 2015 June 7; 21(21): 6470-6478

10. Right versus Left Colon:
Evidence from Literature
King et al. AJHO. 2016;12(10):4-11

11. Right versus Left Colon:
Why different disease entities?
Different:
• Blood Supply
• LN Drainage
1. Embryologic Origin
2. Blood Supply & Nodal Drainage
3. Microbiome Difference
4. Precancerous Lesions.
6. Histopathology & Natural History
5. Consensus Molecular Subtypes.
Stintzing et al. European Journal of Cancer 84 (2017) 69e80

12. 3. Microbiome Difference:
Right Colon Cancer Left Colon Cancer
Prevotella, Pyramido-bacterium,
Selenomonas and Peptostreptococcus.
Fusobacterium, Escherichia-Shigella
and Leptotrichia
Escherichia coli phylogroup B2. Helicobacter pylori infection
Dense Bacterial Aggregates
1. E-Cadherin
2. IL-6
3. STAT3
Cellular
Proliferation
Invasion of Colonic Mucous Layer
Proinflammatory Genes
Flemer et al. Tumour-associated and non-tumour- associated microbiota in colorectal cancer. Gut 2017;66(4): 633e43.

13. 4. Pre-Neoplastic Lesions:
Lee et al. JNCCN—Journal of the National Comprehensive Cancer Network. Volume 15 Number 3. March 2017

14. Lee et al. JNCCN—Journal of the National Comprehensive Cancer Network. Volume 15 Number 3. March 2017
Molecular Alterations in
CRC:

15. Molecular Alterations in
CRC:
Stintzing et al. European Journal of Cancer 84 (2017) 69e80

16. Molecular Alterations in
CRC:
Stintzing et al. European Journal of Cancer 84 (2017) 69e80

17. 5. Consensus Molecular
Subtypes (CMS):
RIGHTCOLONLEFTCOLON
BETTER
OUTCOME
WORSE OUTCOME
Guinney et al. Nature Medicine. 21,1350-1356 (2015)
Lee et al. JNCCN—Journal of the National Comprehensive Cancer
Network. Volume 15 Number 3. March 2017.

18. Parameter Right Colon Left Colon
Gender Female Male
Age Higher Lower
Grade Higher Lower
Mucoid Activity More Prevalent Less Prevalent
Stage Higher Lowe
Spread Peritoneum Liver & Lung
6.Natural History &
Histopathology:
Nitsche et al. Right sided colon cancer as a distinct histopathological subtype with reduced prognosis.
Dig Surg 2016;33(2):157e63.

19. Petrelli et al. Jama Oncology. 2017 Vol 3 Number 2
66 RCT = 1437846 Colon Cancer Patients
Location as an Independent Prognostic Factor:

21. TEJPAR et al. JAMA Oncology February 2017 Volume 3, Number 2

22. TEJPAR et al. JAMA Oncology February 2017 Volume 3, Number 2

23. Right Versus Left Sided Colon
Cancer OAS & Anti-EGFR:
Jhonathan et al. Ther Adv Med Oncol 2017, Vol. 9(8) 551–564

24. Jhonathan et al. Ther Adv Med Oncol 2017, Vol. 9(8) 551–564
Right Versus Left Sided Colon
Cancer PFS & Anti-EGFR:

25. Treatment Platform:
Jhonathan et al. Ther Adv Med Oncol 2017, Vol. 9(8) 551–564

26. Take Home Message:
• Tumor location in mCRC has prognostic and
predictive implication.
• Right colon cancer is doing much worse than
left colon across treatment trials.
• Anti-EGFR directed therapies in RAS wild
patients should not be used for patients with
right sided colon cancer.
• Significant survival benefit was confirmed for
both Anti-EGFR and Anti-VEGF directed
therapies for left sided lesions.
• Bevacizumab is beneficial in right sided colon
cancer particularly if BRAF mutation is present.

27. Thank You