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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
“Impact of aspirin as secondary preven3on in an unselected cohort of
25,644 pa3ents with colorectal cancer: A popula3on-‐based study”
DM: ”ASCO debuterte foran 5000”
Simer Bains, MD Norsk senter for molekylærmedisin
Universitetet i Oslo
Avd for kreFbehandling OUS
• 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 Mul3variate • HR 0.86 • 95% CI 0.81 – 0.91, • p < 0.001
Colorectal cancer survival Mul3variate • HR 0.75 • 95% CI 0.70 – 0.81, • p < 0.001
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
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.
“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”
Maria Thomsen Overlege og sMpendiat Avd for kreFbehandling
OUS
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
Presented By Salvatore Siena at 2015 ASCO Annual Meeting
Ca 5% ved CRC
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
