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
Me Before Me After 292 Posters
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
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
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
STEAM: RR cfolfoxiri- BEV (n=93) sfolfoxiri- BEV (n=92) Pooled FOLFOXIRI- BEV (n=185) FOLFOX- BEV (n=95) ORR, % 60.2 62.0 61.1 47.4 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, % 4.3 0 2.2 1.1 PR, % 55.9 62.0 58.9 46.3 SD, % 31.2 32.6 31.9 40.0 PD, % 2.2 1.1 1.6 6.3 Unable to evaluate, % 6.5 4.3 5.4 6.3 Bendell et al. ASCO GI 2016
STEAM: PFS Hurwitz et al. ASCO GI 2017 #657
FOLFOXIRI+BV all over the world Study Phase N RR% PFS OS STEAM II 185 (s+c) 61% 11.7 34.0 CHARTA II 121 70% 12.0 28.0 TRIBE III 252 65% 12.3 29.8 OLIVIA II 41 81% 18.6 NR
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
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
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
Durable responses Hurwitz et al. ASCO GI 2017 #676
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% 10.3 68% 5.7 14.0 Heracles Trastuz+L apat 27 30% 9.5 59% 5.3 11.5 Hurwitz et al. ASCO GI 2017 #676 Sartore-Bianchi et al. Lancet Oncol 2016
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
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-1 1-3 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
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
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
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
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
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
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 2.0 4.4 HR=0.42 (95%CI 0.26-0.66) p=0.0002 Kopetz et al. ASCO GI 2017 #520 Tumor cell proliferation and survival P P Raf MEK Erk
Alternative approaches with panrafi Sorokin et al. ASCO GI 2017 #616
that overcomes resistance Sorokin et al. ASCO GI 2017 #616
Future new targets
ALK, ROS, NTRKs rearranged: a new mcrc subtype Pietrantonio et al. ASCO GI 2017 #589
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
For each molecular track A personalized treatment
Thank you for your attention!!! salvatore.lisa82@gmail.com