case presentation: management of lld of colorectal cancer origin
TRANSCRIPT
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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
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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.”
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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.
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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
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Case Study: 47-Year-Old Female With mCRC: Therapeutic Strategy
MDT Indicated for Conversion Therapy
Definitive Surgical Intervention
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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:
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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?
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Tumor• Resectability• Biology• Symptoms
Treatment• Efficacy• Toxicity• Availability
Patient• Age• PS• Comorbidities• Preference
Factors Affecting Choice of 1st Line Treatment
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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:
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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
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•STEATOSIS
➨ 5FU
•STEATOHEPATITIS
➨ Irinotecan
•SINUSOIDAL OBSTRUCTION
➨ Oxaliplatin
Systemic Therapy Induced Liver Injury:
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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:
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Choice of Systemic Therapy
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Choice of Systemic Therapy:
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Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015
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Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015
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Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015
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Choice of Systemic Therapy:
Khattak et al. Clinical Colorectal Cancer, Vol. 14, No 2, 81 – 90. 2015
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Role for bevacizumab in increasing resectability?
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Anti-EGFR Therapy Improves Resection Rates
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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
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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).
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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.
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Thank you