ADVANCES IN COLON CANCER

Transcription

1 ADVANCES IN COLON CANCER Peter T. Silberstein, M.D., FACP Professor, Creighton University Chief Hematology/Oncology UNIVERSAL SCREENING FOR LYNCH SYNDROME OF ALL PATIENTS WITH COLON CANCER ADOPTED BY CHI UNIVERSITY OF NEBRASKA FAMILY HISTORY NOT ACCURATE ENOUGH TO DETECT ALL CASES LYNCH SYNDROME SOME PATIENTS WITH LYNCH SYNDROME HAVE NO RELATIVES WITH COLON CANCER. 1

2 ALGORITHM UNIVERSAL SCREENING MSI (MICROSATELLITE INSTABLE) IHC (IMMUNOHISTOCHEMISTRY) FOR MISMATCH REPAIR GENES HALF OF ABNORMALITIES OF MISMATCH REPAIR GENES ARE SOMATIC, AND HALF GENETIC TO CONFIRM LYNCH SYNDROME MUST SEQUENCE PATIENTS BLOOD DURATION OF ADJUVANT CHEMOTHERAPY LOW RISK T1 TO T3, N1 3 YEAR DISEASE FREE SURVIVAL 83.3% TO 83.1% LESS NEUROPATHY WITH 3 MONTHS RECOMMEND 3 MONTHS HIGH RISK GIVE 6 MONTHS CHEMOTHERAPY T4, N2 3 YEAR DISEASE FREE SURVIVAL 64.4% VS. 62.7% 2

3 AMERICAN CANCER SOCIETY START COLON CANCER SCREENING AGE 45 RATES OF COLON CANCER AGE INCREASE 1.5% PER YEAR AGE INCREASE 1% PER YEAR 3

4 NO INCREASE AGE DECREASE AGE ETIOLOGY UNCLEAR WHY INCREASE YOUNGER PEOPLE GETTING COLON CANCER MAY BE THE AMERICAN DIET, AND OBESITY 4

5 DIET AND COLON CANCER JAPANESE MIGRANTS WITHIN ONE GENERATION HAVE SAME INCREASED RISK OF COLON CANCER AS AMERICANS PRESUMABLY SECONDARY TO DIET IMMUNE CHECKPOINT INHIBITORS Goyal G, Silberstein PT. Systemic Therapy in Metastatic Melanoma Fed Pract May;32:5(suppl 4):57S-65S. 5

6 Immune Therapy Only helpful Lynch Syndrome (or MSI high) Ineffective majority metastatic colon cancer Anti PD1 therapy (3 drugs) Major new advances in cancer care last several years Approved head neck cancer, lung cancer, Hodgkin s, melanoma, renal cell, bladder cancer, liver cancer, stomach cancer, Merkel Cell Clinical Benefit of Pembrolizumab Treatment According to Mismatch-Repair Status. Le DT et al. N Engl J Med 2015;372:

7 Biological Agents Bevacizumab Antibody VEGF Vascular Endothelial Growth Factor (Angiogenesis) Antibody to EGFR1 -- Cetuximab Panitumumab Only works in KRAS, NRAS wild type VEGF Trap Aflibercept Drug price reduced due protest Memorial Sloan Kettering KRAS MUTATION Colorectal Cancer 7

8 KRAS, NRAS 40% to 45% of CRC patients KRAS, NRAS downstream of EGFR When either KRAS or NRAS gene is mutated and constitutively active regardless of EGFR activation Then inhibition of EGFR has no clinical effect Mendelsohn J, et al. Oncogene. 2000;19: Khambata-Ford S, et al. J Clin Oncol. 2007;25: COLORECTAL CANCER TREATED WITH CETUXIMAB (ANTI-EGFR AB) KRAS status KRAS mutation Median PFS (95% CI), n = weeks (8-16) Wild type 31.4 weeks ( ) Median OS (95% CI), n = months (5.1-13) 14.3 months (9.4-20) P Value Lièvre A, et al. J Clin Oncol. 2008;26:

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10 EGFR antibodies (Cetuximab, Panitumumab) Acne-form rash Diarrhea Anti angiogenesis VEGF antibody (Bevacizumab, Aflibercept) Wound healing Hold surgery including port, 4-6 weeks prior to after giving drugs Vascular events, bowel perforation,hypertension FOLFOX 5FU, Leucovorin, Oxalaplatin FOLFIRI 5FU, Leucovorin Irinotecan Side effect diarrhea Same 46 hour schedule with home pump as Folfox Capecitabine Oral 5FU More convenient Side effects; Diarrhea, hand foot syndrome Better tolerated in Europe 10

11 Stage IV metastatic colon cancer Left sided Right Sided median survival 33 months median survival 19 months SURVIVAL WITH CHEMOTHERAPY Left sided Cetuximab (36 months); Bevacizumab (31 months) Right sided Bevacizumab (24 months); Cetuximab (17 months) Overall, no difference survival cetuximab, bevacizumab New Oral Agents Metastatic Colon Cancer Multi-kinase inhibitor Regorafenib 1.4 month overall survival advantage Hand foot syndrome/diarrhea/fatigue Oral (trifluridine and tipiracil) Lonsurf 1.8 months overall survival Statistically improvement in survival Questionable clinically important improvement in survival 11

12 Folfox Folfiri EGFR antibodies (if full Ras wild type) Panitumumab Cetuximab Anti VEGF Bevacizumab? Continue and change chemotherapy if progression Aflibercept (second line only) Many doctors continue chemotherapy until progression Drop oxaliplatin when neuropathy bothersome 12

13 Survival Stage IV Colon Cancer Asymptomatic No Chemotherapy Median Survival 5 months Old Chemotherapy 5-FU, LV Chemotherapy Median Survival 11 months New Chemotherapy and Biological agents Median Survival months Prospective, non randomized study, Nurses Health Study 573 women post surgery Excluded those died within 24 months Prediagnosis physical activity not related mortality 50% reduction in Colorectal deaths Any cause death Those that walked equivalent 6 hours per week 13

14 No improvement in survival With Healthy Eating 14