Describes the management of metastatic colorectal cancer to liver only. The role of anti-EGFR and anti VEGF

1. Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
Multidisciplinary Management
of Colon Cancer with Liver
Limited Metastases.
ACOD 2015 - Amgen Symposium
Helnan Palestine Hotel
22/10/2015

2. Speaker Disclosures & Amgen
Disclaimers
Speaker Disclosures
Member of Advisory Board, Consultant, and Speaker for:
● Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen
Cilag, Merck Serono, Novartis, Pfizer
Amgen Disclaimers
● “The scientific information presented and discussed at this
event may or may not be approved in your country of
residence; we recommend consulting the prescribing
information approved.
● Amgen only recommends the use of their products according to
the prescribing information approved by local regulatory
authorities.”

3. Case Study: 47-Year-Old Female With mCRC
Presentation
● 47 years old, female
● History of vague abdominal pain with progressive
constipation, bleeding per rectum since 06/2014
and right hypochondrial tenderness on
examination.

4. Case Study: 47-Year-Old Female With
mCRC Diagnosis
Aug/2014
● Lower GI Endoscopy
– Mass at the recto-sigmoid junction
– Friable, necrotic and easily bleeding on touch
– Further passage was not possible, biopsies were taken
● CT scan
– Dilated bowel loops above recto-sigmoid junction
– Multiple hepatic deposits beyond immediate intervention
Aug/2014
● Palliative colostomy to prevent obstruction
– As the patient was about to be obstructed, she first underwent a temporary
divergent colostomy prior to initiation of systemic treatment
● RAS test
– Wild type on extended RAS testing
– The tissue specimen was obtained from the PRIMARY LESION via endoscopic
biopsy

5. Case Study: 47-Year-Old Female With
mCRC: Therapeutic Strategy
MDT  Indicated for Conversion Therapy
Definitive Surgical Intervention

6. Survival (%)
Author (year) No. Patients Mortality,% Median Survival 1-year 5-year
Hughes et al (86) 607 --- --- --- 33
Gayowski et al (94) 204 0 33 mo 91 32
Scheele et al (95) 469 4 40 mo 83 39
Fong et al (95) 577 4 40 mo 85 35
Jamison et al (97) 280 4 33 mo 84 27
Fong et al (99)
Choti et al (02)
Pawlik et al (05)
1001
226
557
3
1
1
42 mo
46 mo
74 mo
---
96
97
36
40
58
Hughes KS, et al. Surgery. 1986;100(2):278-284. Gayowski TJ, et al. Surgery. 1994;116(4):703-710. Scheele J, et al. World J Surg.
1995;19(1):59-71. Fong Y, et al. Ann Surg. 1995;222(4):426-434.; Jamison RL, et al. Arch Surg. 1997;132:505–510. Fong Y, et al. Ann Surg
1999;230:309-318; Choti MA, et al. Ann Surg. 2002;235(6):759-766; Pawlik TM, et al. Ann Surg. 2005;241(5):715-722.
Results of Hepatic Resection for Patients
with mCRC:

7. Case Study: 47-Year-Old Female With
mCRC: Choice of 1st Line Treatment:
1. Oxaliplatin or Irinotecan Based Duplet Chemotherapy?
2. Triplet Chemotherapy?
3. Duplet + Anti-EGFR?
4. Duplet + Anti-VEGF?
5. Triplet + Anti-VEGF?

8. Tumor
• Resectability
• Biology
• Symptoms
Treatment
• Efficacy
• Toxicity
• Availability
Patient
• Age
• PS
• Comorbidities
• Preference
Factors Affecting Choice of 1st Line
Treatment

9. It’s MANDATORY!
 Greater accuracy of staging
 Fewer treatment delays
 Better outcome!
Fleissing A, et al. Lancet Oncol. 2006; 7(11): 935 – 943; Du CZ, et al. Worl J Gastroenterol. 2011;17(15):2013-2018;
MacDermid E, et al. Colorectal Dis. 2009;11(3):291-295; Viganò L, et al. Ann Surg Oncol. 2013 Mar;20(3):938-45
Early MDT Evaluation:

10. Choice of Systemic Therapy:
Selected Treatment Should Offer:
1. Highest Possible Response Rate  Optimal Shrinkage.
2. Prevention of Disease Progression.
3. Eradication of Micro-Metastatic Disease  If Any.
4. Least Hepatic Toxicity.
Complete Radiologic Response Should not be Warranted

11. •STEATOSIS
➨ 5FU
•STEATOHEPATITIS
➨ Irinotecan
•SINUSOIDAL OBSTRUCTION
➨ Oxaliplatin
Systemic Therapy Induced Liver Injury:

12. Median OS
Months
1980s 1990s 2000s
BSC
5-FU
Irinotecan1
Capecitabine2
Oxaliplatin3
Bevacizumab4
Cetuximab5,6
Panitumumab
7 Aflibercept8
Regorafenib
9
30
25
20
15
10
5
0
1. Cunningham D, et al. Lancet. 1998;352(9138):1413-1418. 2. Van Cutsem E, et al. Br J Cancer.
2004;90(6):1190-1197. 3. Rothenberg M, et al. J Clin Oncol. 2003;21(11):2059-2069.
4. Hurwitz H, et al. N Engl J Med. 2004;350(23):2335-2342. 5. Cunningham D, et al. N Engl J Med.
2004;351(4):337-345. 6. Van Cutsem E, et al. N Engl J Med. 2009;360(14):1408-1417.
7. Van Cutsem E, et al. J Clin Oncol. 2007;25(13):1658-6164. 8. Van Cutsem E et al. J Clin Oncol.
2012;30(28):3499-3506. 9. Grothey A, et al. Lancet. 2013;381(9863):303-312.
Choice of Systemic Therapy:

13. Choice of Systemic Therapy

14. Choice of Systemic Therapy:

15. Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

16. Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

17. Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

18. Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

19. Role for bevacizumab in increasing resectability?

20. Anti-EGFR Therapy Improves Resection Rates

21. Case Study: 47-Year-Old Female With
mCRC 1st-line treatment
Aug/2014
● Panitumumab 6 mg/kg every 2 weeks + FOLFOX
– FOLFOX + panitumumab therapy was considered as a step
forward for conversion to achieve R0 resection
● It has to be taken into consideration that our patient had
distal colonic disease, and our goal was to achieve cure
through conversion therapy. In other words, we were in a
race to achieve the highest possible RESPONSE RATE,
so targeted therapies in addition to the 1st-line
chemotherapy backbone were warranted
FOLFOX = leucovorin-5-fluorouracil-oxaliplatin

22. Case Study: 47-Year-Old Female With
mCRC 1st-line treatment
Dec/2014
● PET-CT scan post-treatment assessment
– Decreased number and size of liver deposits (4) of maximum 20
mm in diameter, not interfering with biliary or vascular pedicles
– Patient underwent formal resection/anastomosis of the primary
tumor and combined resection/open RFA of liver deposits.
– Patient received FOLFOX X 3 months.
● Patient is now free of disease on last assessment (1
month ago).

23. Conclusions For Today
● Meta-analysis of RCT indicated better RR & OAS benefit
for anti-EGFR over anti-VEGF therapies with equivocal
PFS effect in mCRC.
● Full RAS assessment for all newly diagnosed advanced
and/or metastatic CRC should be considered.
● First-line anti-EGFR therapy may be a real alternative to
anti- VEGF therapy as initial treatment of advanced
CRC.