Colon Cancer ASCO Poster Review

Transcription

1 Rome, February 11 th 2017 AIOM POST ASCO GI Review Colon Cancer ASCO Poster Review Lisa Salvatore UOC Oncologia Policlinico GB Rossi Azienda Ospedaliero Universitaria Integrata di Verona

2 Me Before Me After 292 Posters

3 My personal selection Combo of old drugs The Triplet New Drugs/Combo for Old Targets BRAF inhibitor Treatment of mcrc New Drugs/Combo for New targets HER2 inhibitor Immuno-therapy MSI

4 My personal selection Combo of old drugs The Triplet New Drugs/Combo for Old Targets BRAF inhibitor Treatment of mcrc New Drugs/Combo for New targets HER2 inhibitor Immuno-therapy MSI

5 STEAM: updated results Phase II study Primary endpoints ORR1 cfolfoxiri+bv vs FOLFOX+BV PFS1 pooled FOLFOXIRI+BV vs FOLFOX+BV Hurwitz et al. ASCO GI 2017 #657

6 STEAM: RR cfolfoxiri- BEV (n=93) sfolfoxiri- BEV (n=92) Pooled FOLFOXIRI- BEV (n=185) FOLFOX- BEV (n=95) ORR, % Odds ratio vs FOLFOX-BEV (90% CI) b 1.7 (1.05, 2.77) p=0.075 c 1.8 (1.12, 2.97) p=0.040 c 1.8 (1.16, 2.68) p=0.025 c CR, % PR, % SD, % PD, % Unable to evaluate, % Bendell et al. ASCO GI 2016

7 STEAM: PFS Hurwitz et al. ASCO GI 2017 #657

8 FOLFOXIRI+BV all over the world Study Phase N RR% PFS OS STEAM II 185 (s+c) 61% CHARTA II % TRIBE III % OLIVIA II 41 81% 18.6 NR

9 My personal selection Combo of old drugs The Triplet New Drugs/Combo for Old Targets BRAF inhibitor Treatment of mcrc New Drugs/Combo for New targets HER2 inhibitor Immuno-therapy MSI

10 Hurwitz et al. ASCO GI 2017 #676 MyPathway study HER-2 BRAF Hedgehog EGFR Overexpression or mutation V600E or other mutations SMO-activ mut PTCH-1 loss Activating mut Trastuzumab + pertuzumab Vemurafenib Vismodegib Erlotinib By courtesy of Chiara Cremolini

11 Response rate N=31 RR 38.2% CBR 50% RR KRAS wt vs mut: 52% vs 0% RR left/rectum vs right: 42.9%/45.5% vs 12.5% Hurwitz et al. ASCO GI 2017 #676

12 Durable responses Hurwitz et al. ASCO GI 2017 #676

13 HER2: a new target Study Tx KRAS wt N RR % Median duration of response DCR % PFS mos OS mos MyPathwa y Trastuz+P ertuz 25 52% % Heracles Trastuz+L apat 27 30% % Hurwitz et al. ASCO GI 2017 #676 Sartore-Bianchi et al. Lancet Oncol 2016

14 My personal selection Combo of old drugs The Triplet New Drugs/Combo for Old Targets BRAF inhibitor Treatment of mcrc New Drugs/Combo for New targets HER2 inhibitor Immuno-therapy MSI

15 Pembro in MSI mcrc The Mayo Clinic experience N (17) % Response at 1 st Scan Complete Response (CR) 1 6% Partial Response (PR) 7 41% Stable Disease (SD) 2 12% Progressive Disease (PD) 4 24% DCR (PR+CR+SD) 10 59% N % Duration of PD cycles 6 35% 4-9 cycles 6 35% 10+ cycles 5 30% Reason to discontinue PD-1 Toxicity/Side Effects 0 0% Progressive Disease 2 12% Death 4 24% Leal et al. ASCO GI 2017 #714

16 Anti-PD1 in MSI mcrc Study Phase Tx N RR % DCR % 1yr-PFS 1yr-OS Mayo Clinic Cohort Pembro 17 47% 59% 64% 75% Keynote-016 II Pembro 11 40% 59% 62% 70% Keynote-142 II Nivo 74 31% 69% 48.4% 73.8% Leal et al. ASCO GI 2017 #714 Le et al. NEJM 2015 Overman et al. ASCO GI 2017 #519

17 And anti-pdl1? Pretreated mcrc Deficient in Mismatch Repair Atezolizumab + Bevacizumab N 10 Phase Ib trial Primary endpoint: safety and tolerability Secondary endpoints: RR, DOR, PFS (RECIST 1.1 and irrc) Hochster et al. ASCO GI 2017 #673

18 Immunotherapy in pretreated MSI mcrc Study Phase Tx N RR % DCR % 1yr-PFS 1yr-OS Mayo Clinic Cohort Pembro 17 47% 59% 64% 75% Keynote-016 II Pembro 11 40% 59% 62% 70% Keynote-142 II Nivo 74 31% 69% 48.4% 73.8% Hochster et al Ib Atezo+BV 10 40% 90% NR NA

19 Ongoing Keynote-177: Pembro in first-line Phase III study N 270 Primary endpoint: PFS per RECIST 1.1 Secondary endpoints: OS, RR (RECIST 1.1) safety Diaz et al. ASCO GI 2017 #TPS815

20 My personal selection Combo of old drugs The Triplet New Drugs/Combo for Old Targets BRAF inhibitor Treatment of mcrc New Drugs/Combo for New targets HER2 inhibitor Immuno-therapy MSI

21 Targeted approaches: BRAFi + EGFRi SWOG S1406 Cet+Iri (N=50) Cet+Iri+Vemu (N=49) Tumor cell EGF RR 4% 16% DCR 22% 67% P P Ras PFS HR=0.42 (95%CI ) p= Kopetz et al. ASCO GI 2017 #520 Tumor cell proliferation and survival P P Raf MEK Erk

22 Alternative approaches with panrafi Sorokin et al. ASCO GI 2017 #616

23 that overcomes resistance Sorokin et al. ASCO GI 2017 #616

24 Future new targets

25 ALK, ROS, NTRKs rearranged: a new mcrc subtype Pietrantonio et al. ASCO GI 2017 #589

26 Take home messages FOLFOXIRI+Bev is a valid option as first-line treatment of mcrc HER2-amplified/overexpressed mcrc can benefit from a specific HER2- targeted therapy Immunotherapy can be a valid option for pretreated MSI mcrc (in first-line it is under evaluation) EGFR pathway inhibition (EGFRi+BRAFi or panrafi) can be an option for BRAF mut mcrc

27 For each molecular track A personalized treatment

28 Thank you for your attention!!!