Alessandro Inno. IRCCS Ospedale Sacro Cuore Don Calabria Negrar, Verona

Transcription

1 GRUPPO C Coordinatore: Diego Signorelli Ruolo dei checkpoint inhibitors nelle neoplasie polmonari: le evidenze scientifiche e l inserimento dei checkpoint inhibitors nell algoritmo decisionale del NSCLC Alessandro Inno IRCCS Ospedale Sacro Cuore Don Calabria Negrar, Verona

2 Immune Checkpoint Inhibitors for NSCLC: 2 nd line and beyond

3 2 nd line Checkpoint inhibitors for NSCLC: summary of evidence Study Phase CheckMate-017 [1] III Nivolumab Pembrolizumab Atezolizumab CheckMate-057 [2] III KEYNOTE-010 [3] II/III OAK [4] III n 135 vs vs vs 346 vs vs Histology SQ (100%) Non-SQ (100%) SQ (21%) Non-SQ (79%) SQ (26%) Non-SQ (74%) PD-L1 All comers All comers TPS 1% All comers IHC test target Schedule 28-8 Dako TC 3 mg/kg Q 14d Control Arm Docetaxel 75 mg/m 2 Q 21d 28-8 Dako TC 3 mg/kg Q 14d Docetaxel 75 mg/m 2 Q 21d Line 100% 2nd 88% 2nd 11% 3rd mos 9.2 vs 6.0 HR 0.59, p< vs 9.4 HR 0.73, p= C3 Dako TC 2 mg/kg, 10 mg/kg Q 21d Docetaxel 75 mg/m 2 Q 21d 69% 2nd 20% 3rd 10.4 vs 12.7 vs 8.5 HR 0.71, p=0.0008* SP 142 Ventana TC and IC 1200 mg Q 21d Docetaxel 75 mg/m 2 Q 21d 75% 2nd 25% 3rd 13.8 vs 9.6 HR 0.73, p= yr survival 42% vs 24% 51% vs 39% 43.2% vs 52.3% vs 34.6% 55% vs 41% mpfs 3.5 vs 2.8 HR 0.62, p< vs vs 4.0 vs vs 4.0 RR 20% vs 9% 19% vs 12% 18% vs 18% vs 9% 14% vs 13% TRAEs G3 7% vs 55% 10% vs 54% 13% vs 16% vs 35% 15% vs 43% *pembrolizumab 2 mg/kg vs docetaxel; + primary analysis population 1) Brahmer J, et al. N Engl J Med 2015;373(2): ) Borghaei H, et al. N Engl J Med 2015;373(17): ) Herbst RS, et al. Lancet 2016;387(10027): ) Rittmeyer A, et al. Lancet 2017;389(10066):

4 2 nd line Checkpoint inhibitors for NSCLC: a consistent benefit in OS Vokes EE et al. Ann Oncol 2018;29(4): Herbst RS, et al. Lancet 2016;387(10027): Rittmeyer A, et al. Lancet 2017;389(10066):

5 2 nd line Checkpoint inhibitors for NSCLC: PD-L1 expression Checkmate 017 [1] KEYNOTE 001 [3] Checkmate 057 [2] OAK [4] 1) Brahmer J, et al. N Engl J Med 2015;373(2): ) Borghaei H, et al. N Engl J Med 2015;373(17): ) Herbst RS, et al. Lancet 2016;387(10027): ) Rittmeyer A, et al. Lancet 2017;389(10066):

6 How long to treat? Continuous vs fixed duration Treatment beyond progression

7 CheckMate 153: continuous vs 1-year fixed duration nivolumab Spigel DR, et al. Ann Oncol 2017;28(Suppl5): Abstract 1297O.

8 CheckMate 153: continuous vs 1-year fixed duration nivolumab PFS from randomization Response status PFS HR (95% CI) CR/PR 0.45 ( ) SD 0.44 ( ) OS from randomization Spigel DR, et al. Ann Oncol 2017;28(Suppl5): Abstract 1297O.

9 OAK: OS post-pd in the atezolizumab arm by post-pd treatment Gandara R, et al. ASCO Abstract #9001

10 Immune Checkpoint Inhibitors: 1 st line

11 KEYNOTE-024: study design Reck M, et al. N Engl J Med 2016;375(19):

12 KEYNOTE-024: PFS and RR Reck M, et al. N Engl J Med 2016;375(19):

13 KEYNOTE-024: Updated OS results (median follow-up 19.1 months) Kaplan-Meier Estimate of OS: <br />Updated Analysis Presented By Julie Brahmer at 2017 ASCO Annual Meeting

14 NSCLC avanzato: algoritmo decisionale in Italia nel 2018 Non-Squamous NSCLC Squamous NSCLC EGFR/ALK/ROS1+ EGFR/ALK/ROS1- PDL1 <50% EGFR/ALK/ ROS1- PDL1 50% PDL1 50% PDL1<50% 1st line TKIs Platinum doublet +/-Bevacizumab Maintenance Pembrolizumab Platinum doublet 2nd line Nivolumab/Atezolizumab Pembrolizumab if PDL1>1% Docetaxel +/- nintedanib Platinum doublet +/-Bevacizumab Maintenance Platinum doublet Nivolumab/Atezolizumab Pembrolizumab if PDL1>1% Docetaxel

15 The (next) future: 1st-line ICI for PDL1 <50%? Biomarkers (TMB) Combinations ICI + Chemo ICI + Chemo + anti-vegf ICI + ICI

16 KEYNOTE-042: study design Presented By Gilberto Lopes at 2018 ASCO Annual Meeting

17 KEYNOTE-042: OS OS TPS 50% OS TPS 20% OS TPS 1% Lopes G, ASCO 2018.

18 KEYNOTE-042: OS Presented By Gilberto Lopes at 2018 ASCO Annual Meeting

19 KEYNOTE-189 KEYNOTE-189 & KEYNOTE-407: study designs Primary Endpoints: - PSF - OS Gandhi L, et al. N Engl J Med 2018;378(22): KEYNOTE-407 Paz-Ares LG, et al. ASCO 2018

20 KEYNOTE-189 KEYNOTE-189 & KEYNOTE-407: OS data Gandhi L, et al. N Engl J Med 2018;378(22): KEYNOTE-407 Paz-Ares LG, et al. ASCO 2018

21 IMpower131 Jotte R, ASCO 2018

22 IMpower131: Atezolizumab+CnP vs CnP in SQ-NSCLC Jotte R, et al. ASCO 2018

23 IMpower150: study design Socinski MA, et al. N Engl J Med 2018;378(24):

24 IMpower150: OS in ITT-WT and Key subgroups Socinski MA, et al. N Engl J Med 2018;378(24):

25 CheckMate 227 Co-primary End Points for Nivolumab plus Ipilimumab vs. Chemotherapy: Progression-free survival in populations selected on the basis of TMB Overall survival in populations selected on the basis of PD-L1 expression Hellmann MD, et al. N Engl J Med 2018;378(22):

26 CheckMate 227: PFS in patients with high TMB Hellmann MD, et al. N Engl J Med 2018;378(22):

27 CheckMate 227: exploratory analysis in PDL1 <1% PFS: Nivolumab + Chemotherapy and Nivolumab + Ipilimumab <br />By TMB Presented By Hossein Borghaei at 2018 ASCO Annual Meeting

28 1 st line Checkpoint inhibitors for NSCLC: summary of evidence

29 Immune Checkpoint Inhibitors: Stage III

30 PACIFIC trial: study design Antonia SJ, et al. N Engl J Med 2017;377(20):

31 PACIFIC trial: PFS by BIRC Antonia SJ, et al. N Engl J Med 2017;377(20):

32 PACIFIC trial: safety Antonia SJ, et al. N Engl J Med 2017;377(20):

33 Aknowledgments

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