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ASCO 2015 Noen høydepunkter fra GI Morten Brændengen MD, PhD Overlege, seksjonsleder Avd for kreFbehandling Oslo universitetssykehus • 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 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” • Retrospek3v cohort-‐studie • Registrering av follow up eEer CRC og bruk av aspirin • Uselektert materiale av CRC pasienter fra 2004-‐2011 ved bruk av KreKregisteret og Resept registeret • N= 25644 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. Results Overall survival Colorectal cancer survival Mul3variate • HR 0.86 • 95% CI 0.81 – 0.91, • p < 0.001 Mul3variate • HR 0.75 • 95% CI 0.70 – 0.81, • p < 0.001 Strenghts and limita3ons 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 – Non-‐randomized data – Over-‐the-‐counter use – COX-‐2 levels and PI3KCA mutaMons – Short follow-‐up Mme 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. 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” Sterk korrelasjon mellom CRP og IL-‐6 Pretreatment levels of CRP and IL-‐6 were assosiated with impaired overall survival 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. 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 ASCO Recommendations<br />Benson et al: ASCO Consensus Statement JCO 2004 Presented By Zsofia Stadler at 2015 ASCO Annual Meeting Defective DNA Mismatch Repair Presented By Zsofia Stadler at 2015 ASCO Annual Meeting Future of Adjuvant Therapy (1) <br />IDEA Duration of Therapy Presented By Hanna Sanoff at 2015 ASCO Annual Meeting Immunterapi CRC • MSI – microsatelite instability – Mismatch-‐repair deficient CRC have 10-‐100 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 Mutations per tumor Presented By Dung Le at 2015 ASCO Annual Meeting Slide 8 Presented By Dung Le at 2015 ASCO Annual Meeting Slide 12 Presented By Dung Le at 2015 ASCO Annual Meeting PD-‐1 inhibi3on other GI cancers • HCC (nivolumab, abstr 101) • Øsofagus (pembrolizumab, abstr 4010) • Gastric (pembrolizumab, abstr 4001) 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 Selective Internal Radiation Therapy (SIRT) Presented By Peter Gibbs at 2015 ASCO Annual Meeting Study Design Presented By Peter Gibbs at 2015 ASCO Annual Meeting Progression-Free Survival at Any Site Presented By Peter Gibbs at 2015 ASCO Annual Meeting Progression-Free Survival in the Liver Presented By Peter Gibbs at 2015 ASCO Annual Meeting Conclusions Presented By Peter Gibbs at 2015 ASCO Annual Meeting Therapeutic Dual Inhibition of HER2 Pathway<br />in Metastatic Colorectal Cancer <br />The HERACLES Trial * Presented By Salvatore Siena at 2015 ASCO Annual Meeting HERACLES Diagnostic Criteria Ca 5% ved CRC Presented By Salvatore Siena at 2015 ASCO Annual Meeting Time to Progression by HER2 score Presented By Salvatore Siena at 2015 ASCO Annual Meeting Conclusions of HERACLES Trial Presented By Salvatore Siena at 2015 ASCO Annual Meeting 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 ”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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