Treatment of patients with pancreatic cancer in DK Focus on LAPC and mPC Per Pfeiffer, MD, PhD Professor in Clinical Oncology Dept of Oncology, OUH, Denmark.

Præsentationer af emnet: "Treatment of patients with pancreatic cancer in DK Focus on LAPC and mPC Per Pfeiffer, MD, PhD Professor in Clinical Oncology Dept of Oncology, OUH, Denmark."— Præsentationens transcript:

1 Treatment of patients with pancreatic cancer in DK Focus on LAPC and mPC Per Pfeiffer, MD, PhD Professor in Clinical Oncology Dept of Oncology, OUH, Denmark Institute of Clinical Research, USD, Denmark

2 Pancreatic cancer Stage and therapy ResectableMetastaticLAPC Resection + Adjuvant Gem CT or CRT CT 5year OS: 25% 6 mo -> 12 mo & Symptom relief 3 mo -> 6 mo & Symptom relief

3 Gemcitabine Gemcitabine + other RANDOMISATIONRANDOMISATION mPC vs LAPC PS CT in non-resectable PC Gem vs other

4 Some randomized trials – Gem vs Gem+ nmOSRR LAPCPS0-1RelapsemAge Berlin et al. JCO 2002 Gem1625.46% 10%71%nr65 Gem + Bolus 5-FU1606.77% Rocha Lima et al JCO 2004 Gem1696.64% 14%76%Nonr Gem + Irinotecan1736.316% Oettle et al Ann Onc 2005 Gem2826.37% 9%90%nr63 Gem + Pemetrexed2836.215% Abou-Alfa JCO 2005 Gem1756.25% 21%52%*%nr63 Gem + Exatecan1746.77% Louvet JCO 2005 Gem1567.117% 31%82%No61 Gem FDR +Oxaliplatin1579.027% Heinemann JCO 2006 Gem1006.08% 20%72%nr65 Gem + Cisplatin987.610% Herrmann JCO 2007 Gem1597.212% 21%53%*%nrnr Gem + Capecitabine1608.415% Poplin et al JCO 2009 Gem2794.96% 10%88%5%63 Gem FDR 2776.210% Gem FDR +Oxaliplatin2765.79% Cunningham JCO 2009 Gem2666.212% 29%81%nr62 Gem + Capecitabine2677.119% Colucci et al JCO 2010 Gem1998.310% 16%83%26%63 Gem + Cisplatin2017.213% 6-720%

5 Some randomized trials – Gem +/- TT nmOSRRLAPCPS0-1RelapsemAge Bramhall et al. BJC 2002 Gem1195.416% 29%86%6%62 Gem + marimastat1205.411% Van Cutsem et al JCO 2004 Gem3476.38% 24%86%12%61 Gem + tipifarnib3416.06% Moore et al JCO 2007 Gem2845.918.0% 24%81%8%64 Gem + Erlotinib2856.24*8.6% Richards et al Ann Onc 2006 Gem887.014% 17%86%51%63 Gem + CI-994866.412% Cascinu et al Lancet Onc 2008 Gem + Cis427.812.2% 27%91%nr62 Gem + Cis + Cet427.517.5% Van Cutsem et al JCO 2009 Gem + E3016.08.6% 0%87%nr61 Gem + Bev + E3067.113.5% Phillip et al JCO 2010 Gem3696.014% 22%87%10%64 Gem + Cet3666.512% Kindler et al JCO 2010 Gem3006.013.1% 16%89%nr64 Gem + Bev3025.711.3% Kindler et al Lancet Onc 2011 Gem3168.3 24%100%nr61 Gem + Axitinib3168.5 6-720%10%

6 Gem FOLFIRINOX FU + Iri + Ox FOLFIRINOX FU + Iri + Ox RANDOMISATIONRANDOMISATION 342 patients mPC PS 0-1 Conroy et al., NEJM 2011; 364: 1817-25 Prodige 4 ACCORD112005-9 CT in mPC Gem vs FOLFIRINOX

7 Conroy; NEJM 2011; n = 342GemFOLFIRINOX No of pts171 Response rate9%32%* Median PFS (months)3.36.4* Median survival (months)6.811.1* Conroy et al., NEJM 2011; 364: 1817-25 CT in mPC Gem vs FOLFIRINOX

8 Gem Abraxane Gem Abraxane RANDOMISATIONRANDOMISATION 861 patients mPC PS 0-1 Von Hoff et al., NEJM 2013 MPACT2009-12 CT in mPC Gem vs Gem-Abraxane

9 Von Hoff; NEJM 2013; n = 861GemGem-Abraxane No of pts430431 Response rate invest 8%29%* Median PFS invest (months)3.75.5* Median survival (months)6.78.5* Von Hoff et al., NEJM 2013 CT in mPC Gem vs Gem-Abraxane

10 Bjerregaard …. Pfeiffer. WCGIC 2015 12 Double chemotherapy in non-resectable PC OUH, 2012-14

11 Phase III in non-resectabel PC Burris 1997 PRODIGE Conroy, 2011 MPACT Hoff, 2013 GemS1 OUH Variable Gem n = 63 5-FU n = 63 FOLFIRINOX n = 171 Gem n = 171 nab-P +Gem n = 431 Gem n = 430 GemS1 N=64 Age Median 6261 626368 PS, % 0 003739586225 1 30326261423846 2 7068000029 M1, %7276all 61 RR, %5031929730 PFS, mo2.216.43.35.53.79.0 OS, mo5.74.411.16.88.56.711.7

12 Anbefalinger Patienter med mPC, PS 0-2, bør tilbydes kemoterapi (A) Patienter i god AT, PS 0-1, og uden væsentlig komorbiditet, bør tilbydes kombinationskemoterapi (A) Under hensyntagen til effekt på livstidslængde, bivirkningsprofil og patientønske kan der tilbydes FOLFIRINOX (A) eller Gemcitabin & nab-paclitaxel (A) eller Kombinationsbehandling med gemcitabin (A) Patienter, der skønnes ikke at kunne tåle kombinationsbehandling, men skønnes at tåle enkeltstofbehandling, bør tilbydes gemcitabin (A) 2. linie kemoterapi bør overvejes hos patienter i god AT, PS 0-1 (B) Danish guidelines

13 Danish retrospective study 2 drugs or 3 drugs ? Danish retrospective study in LAPC + M1 3 drugs (FOLFIRINOX, dose ?) 2 drugs (Gemcitabine +) Gemcitabine mono RR, PFS, OS All treating departments will participate 1. meeting Novemver 25th Data fromLPR ? Data will be presented at ØGC 2016 ?

14 Adjuvant therapy with 2 or 3 drugs ? Danish guidelines

15 0 20 40 60 80 100 1 år2 år3 år4 år5 år Surgery + gemcitabin Surgery 25% 15% Pancreatic cancer Adjuvant therapy – CONKO 1 Oettle M et al. JAMA 2007 20 22 1998-2004 n = 355 83% R0

16 0 20 40 60 80 100 1 år2 år3 år4 år5 år Surgery + S-1 Surgery + gemcitabine 45% 26% Pancreatic cancer Adjuvant therapy - JASPAC 1 Uesaka et al. ASCO GI 2013 2007-10 n = 385 87% R0 25 46 22 25%

17 0 20 40 60 80 100 1 år2 år3 år4 år5 år CONKO01 + Gemcitabine DPCG+/- Gemcitabine 25% Pancreatic cancer DPCG – R0/1 resection Oettle M et al. JAMA 2007 20 22 2011-15 n = 379 R0/R1

18 Adjuvant therapy AdjuvantSurgery ⇨ Gemcitabin Gem vs GemCap (ESPAC 4) Gem vs GemAbraxane (APACT) Gem vs FOLFIRINOX (ACCORD) FOLFIRINOX (other?) ⇨ Surgery

19 Pancreatic cancer Stage and therapy ResectableMetastaticLAPC Resection + Adjuvant Gem CT or CRT CT 5year OS: 25% 6 mo -> 12 mo & Symptom relief 3 mo -> 6 mo & Symptom relief

20 Resectability determined by TVI on imaging ResectableResectable with venous resection Resectable with reconstruction Not resectable GroupA1A2B1B2CD SMV PV Free≤50%, ≤2cm encasement >50%, <2cm encasement >50% or 2cm encasement SMA HA CT Free Involve an anomalous artery ≤50%, ≤2cm encasement 50-100%

21 Treatment Schema Presented By Matthew Katz at 2015 ASCO Annual Meeting Presented at ASC0 2015: 22 pts - 14 institutions

22 RECIST Response Presented By Matthew Katz at 2015 ASCO Annual Meeting

23 LAPC-03 Non-resectable Stadie II/III PS 0-1 N=80 MDT Staging FOLFIRINOX 2 months Re-evaluation CT, EUS MDT: Resectability group B-D

24 LAPC-03 Non-resectable Stadie II/III PS 0-1 N=80 MDT Staging FOLFIRINOX 2 months Re-evaluation CT, EUS Resection Resectable FOLFIRINOX 2 months Non-resectable Regression MDT: Resectability group B-D

25 LAPC-03 Non-resectable Stadie II/III PS 0-1 N=80 MDT Staging FOLFIRINOX 2 months Re-evaluation CT, EUS 50Gy/27fx Capecitabine Resection Resectable IRE FOLFIRINOX 2 months Non-resectable Regression Non-resectable No regression Res group B Non-resectable No regression Res group C-D MDT: Resectability group B-D

26 Anbefalinger - LAPC Kemoterapi er førstevalg (A) Kombinationskemoterapi bør tilbydes patienter i god almentilstand FOLFIRINOX eller gemcitabin+ kan anvendes (B) RKT kan tilbydes efter minimum 2 måneders kemoterapi, såfremt det skønnes, at der er mulighed for efterfølgende resektion (C) RKT kan tilbydes efter minimum 2 måneders kemoterapi som alternativ til fortsat kemoterapi (A). Danish guidelines

27 High risk Pancreatic Cancer Optimal treatment CT + CRT Resection

28 Thank you for your attention ??