ASCO 2015 Noen høydepunkter fra GI. Morten Brændengen MD, PhD Overlege, seksjonsleder Avd for krefbehandling Oslo universitetssykehus

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1 ASCO 2015 Noen høydepunkter fra GI Morten Brændengen MD, PhD Overlege, seksjonsleder Avd for krefbehandling Oslo universitetssykehus

2 Sesjoner for øvre, midtre og nedre GI Ingen store nyheter, men mange spennende studier og diskusjoner En rekke abstracts og educamonal sessions CRC Poster 128 Non- CRC Poster 144

3 Simer Bains, MD Norsk senter for molekylærmedisin Universitetet i Oslo Avd for krefbehandling OUS DM: ASCO debuterte foran 5000 Impact of aspirin as secondary preven3on in an unselected cohort of 25,644 pa3ents with colorectal cancer: A popula3on- based study

4 Retrospek3v cohort- studie Registrering av follow up eeer CRC og bruk av aspirin Uselektert materiale av CRC pasienter fra ved bruk av KreKregisteret og Resept registeret N= Effekten av ASA er mest sannsynlig at det bidrar 3l å s3mulere an3tumor- immunitet ved å oppheve Cox- II og prostagladin- E2- indusert hemming av den tumorreeede immunresponsen.

5 Results Overall survival Mul3variate HR % CI , p < Colorectal cancer survival Mul3variate HR % CI , p < 0.001

6 Strenghts and limita3ons Advantages Large number of cases Unselected populamon- based cohort High quality, validated data Complete follow- up- data No recall bias No lead- Mme bias Limita3ons Non- randomized data Over- the- counter use COX- 2 levels and PI3KCA mutamons Short follow- up Mme

7 Konklusjon: Pasienter med tykk- eller endetarmskref som har taa aspirin lever signifikant lengre enn de som ikke hadde brukt aspirin. Resultatene ble korrigert for alder, kjønn, stadium, tumor lokalisasjon, differensieringsgrad og annen legemiddelbruk som antas å ha effekt på sykdommen.

8 Maria Thomsen Overlege og smpendiat Avd for krefbehandling OUS C- reacmve protein and interleukin- 6 as markers of systemic inflammatory response and as prognosmc factors for metastamc colorectal cancer. Data from the randomized phase III NORDIC- VII study

9 Sterk korrelasjon mellom CRP og IL- 6

10 Pretreatment levels of CRP and IL- 6 were assosiated with impaired overall survival

11 Conclusion Elevated CRP values were associated with impaired prognosis. The prognosmc significance of CRP was at least equal to that of other markers of Systemic Inflammatory Response (SIR). CRP values were highly correlated with IL- 6 levels.

12 Interessante GI problems3llinger Flere studier av CRC bekrefer neg prognose ved BRAF mutasjon FOLFIRINOX som 1. linje behandling? TRIBE studien BRAF hemmer (fase I vemurafenib/irinotecan/cetuximab) 35% respons videre kliniske studier Adjuvant kjemoterapi ca coli st II/III Stadium II, undergrupper MSI (microsatelite instability) dmmr (deficient in mismatch repair) pmmr (proficient in mismatch repair) 3 mnd vs 6 mnd

13 ASCO Recommendations<br />Benson et al: ASCO Consensus Statement JCO 2004 Presented By Zsofia Stadler at 2015 ASCO Annual Meeting

14 Defective DNA Mismatch Repair Presented By Zsofia Stadler at 2015 ASCO Annual Meeting

15 Future of Adjuvant Therapy (1) <br />IDEA Duration of Therapy Presented By Hanna Sanoff at 2015 ASCO Annual Meeting

16 Immunterapi CRC MSI microsatelite instability Mismatch- repair deficient CRC have x as many somamc mutamons as MMR proficient CRC PD- 1 programmed death (immun checkpoint ) PD- L1 and L2 Expression of programmed death ligands on the surface of tumor cells is an important predicmve biomarker of response to PD- 1 blockade. Pembrolizumab PD- 1 inhibitor Phase 2 study: treatment refractory progressive mcrc

17 Mutations per tumor Presented By Dung Le at 2015 ASCO Annual Meeting

18 Slide 8 Presented By Dung Le at 2015 ASCO Annual Meeting

19 Slide 12 Presented By Dung Le at 2015 ASCO Annual Meeting

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21 PD- 1 inhibi3on other GI cancers HCC (nivolumab, abstr 101) Øsofagus (pembrolizumab, abstr 4010) Gastric (pembrolizumab, abstr 4001)

22 SIRFLOX: Randomized phase III trial comparing first-line mfolfox6 (+bevacizumab) versus mfolfox6 (+bevacizumab) + selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer Presented By Peter Gibbs at 2015 ASCO Annual Meeting

23 Selective Internal Radiation Therapy (SIRT) Presented By Peter Gibbs at 2015 ASCO Annual Meeting

24 Study Design Presented By Peter Gibbs at 2015 ASCO Annual Meeting

25 Progression-Free Survival at Any Site Presented By Peter Gibbs at 2015 ASCO Annual Meeting

26 Progression-Free Survival in the Liver Presented By Peter Gibbs at 2015 ASCO Annual Meeting

27 Conclusions Presented By Peter Gibbs at 2015 ASCO Annual Meeting

28 Therapeutic Dual Inhibition of HER2 Pathway<br />in Metastatic Colorectal Cancer <br />The HERACLES Trial * Presented By Salvatore Siena at 2015 ASCO Annual Meeting

29 HERACLES Diagnostic Criteria Ca 5% ved CRC Presented By Salvatore Siena at 2015 ASCO Annual Meeting

30 Time to Progression by HER2 score Presented By Salvatore Siena at 2015 ASCO Annual Meeting

31 Conclusions of HERACLES Trial Presented By Salvatore Siena at 2015 ASCO Annual Meeting

32 MET reseptor MetGastric MET reseptor binder hapatocyt growth factor (HGF) D. Cunningham presenterte fase 2 studie med FOLFOX 6 ved ventrikkelcancer (HER 2 neg, MET pos) Ingen effekt av Mllegg med Onartuzumab (MET hemmer) vedr overlevelse. NegaMve resultater også i 2 andre GI studier

33 Nega3ve GI studier XELIRI/FOLFIRI +/- simvastamn Ingen Mlleggs effekt PerioperaMve (3+3 kurer) ECX +/- panitumumab (EGFR hemmer) ved lokalt avansert gastro- esofageal cancer Ingen Mlleggs effekt Gemcitabine + CisplaMn (GemCis) +/- panitumumab ved avansert galleveis cancer Ingen Mlleggs effekt Gemcitabine + Capecitabine (GemCap) +/- Bevazicumab ved avansert galleveis cancer Ikke bedre effekt enn GemCis som standard behandling

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