case presentation: management of lld of colorectal cancer origin
TRANSCRIPT
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