Mohamed Abdulla M.D.

Prof. of Clinical Oncology

Cairo University

Multidisciplinary Management of Colon Cancer with Liver Limited Metastases.

ACOD 2015 - Amgen SymposiumHelnan Palestine Hotel22/10/2015

Speaker Disclosures & Amgen DisclaimersSpeaker DisclosuresMember 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.”

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.

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

Case Study: 47-Year-Old Female With mCRC: Therapeutic Strategy

MDT Indicated for Conversion Therapy

Definitive Surgical Intervention

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

--- 9697

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:

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?

Tumor• Resectability• Biology• Symptoms

Treatment• Efficacy• Toxicity• Availability

Patient• Age• PS• Comorbidities• Preference

Factors Affecting Choice of 1st Line Treatment

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:

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

•STEATOSIS

➨ 5FU

•STEATOHEPATITIS

➨ Irinotecan

•SINUSOIDAL OBSTRUCTION

➨ Oxaliplatin

Systemic Therapy Induced Liver Injury:

Median OSMonths

1980s 1990s 2000sBSC

5-FUIrinotecan1

Capecitabine2

Oxaliplatin3

Bevacizumab4

Cetuximab5,6

Panitumumab7

Aflibercept8

Regorafenib9

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:

Choice of Systemic Therapy

Choice of Systemic Therapy:

Choice of Systemic Therapy:

Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

Choice of Systemic Therapy:

Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

Choice of Systemic Therapy:

Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

Choice of Systemic Therapy:

Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015

Role for bevacizumab in increasing resectability?

Anti-EGFR Therapy Improves Resection Rates

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

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).

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.

Thank you