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Camogli, 29 apr 2016. L’immunoterapia per pochi selezionati pazienti. D. Cortinovis S.C. Oncologia Medica H S. Gerardo Monza. AGENDA. LOOKING FOR A BIOMARKER CLUES IN THE CLINICAL SETTING BEYOND THE CLINICAL PERSPECTIVE. AGENDA. LOOKING FOR A BIOMARKER
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Camogli, 29 apr 2016 L’immunoterapia per pochi selezionati pazienti D. Cortinovis S.C. Oncologia Medica H S. Gerardo Monza
AGENDA • LOOKING FOR A BIOMARKER • CLUES IN THE CLINICAL SETTING • BEYOND THE CLINICAL PERSPECTIVE
AGENDA • LOOKING FOR A BIOMARKER • CLUES IN THE CLINICAL SETTING • BEYOND THE CLINICAL PERSPECTIVE
VS Pennel vs Lisberg JAMA ONCOL 2016
IS PDL1 A GOOD CANDIDATE? Garon NEJM 2015
PEMBROLIZUMAB: KEYNOTE 010 Herbst Lancet 2015
PEMBROLIZUMAB: PDL1>>EFFICACY PDL1> 1% PDL1> 50% Herbst Lancet 2015
PDL1>> NO DISCORDANT mPFS PDL1> 50% PDL1> 1% Herbst Lancet 2015
PDL1 EXPRESSION AND ORR Garon NEJM 2015
ATEZOLIZUMAB: POPLAR Fehrenbacher LANCET 2016
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DURVALUMAB EARLY TRIALS Rizvi ASCO 2015
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MULTIFACTORIAL BIOMARKER InoueOncotarget 2016 TopalianNatCancerRev 2016
AGENDA • LOOKING FOR A BIOMARKER • CLUES IN THE CLINICAL SETTING • BEYOND THE CLINICAL PERSPECTIVE
Smoking status and response to immunotherapy in NSCLC In studies of nivolumab, a history of smoking in patients with NSCLC was associated with improved clinical response and PFS 100 PFS by smoking exposure 80 ≤5 pack-yrs smokers (mPFS 1.7 months) >5 pack-yrs smokers (mPFS 2.2 months)HR (95% CI) = 0.41 (0.22, 0.74), P = 0.003 60 40 PFS (%) 20 0 0 6 12 18 24 30 Months Since Treatment Initiation ≤5 pack-yrs smokers 14 3 1 1 1 1 >5 pack-yrs smokers 75 28 16 12 7 1 HR = hazard ratio; mPFS = median progression-free survival; ORR = objective response rate; PFS = progression-free survival. Hellmann MD, et al. Poster presented at ESMO 2014 (asbtr. 1229PD).
MPDL3280A Phase Ia: Response by Smoking and Mutational Status Smoking Status (NSCLC; n = 53) Response by Smoking Status (ORRa) Former / Current Smokers Pts With PR, % 1/10 11/43 Never Smokers Response by EGFR Status (ORRa) EGFR Status (NSCLC; n = 53) Pts With PR, % Unknown 9/40 1/6 EGFR Mutant Response by KRAS Status (ORRa) KRAS Status (NSCLC; n = 53) Unknown Pts With PR, % 1/10 8/27 KRAS Mutant a ORR includes investigator-assessed u/c PR by RECIST 1.1. Patients first dosed at 1-20 mg/kg by Oct 1, 2012. Data cutoff: Apr 30, 2013.
EGFR OVEREXPRESSION AND MHC I LOSS Herbst Lancet 2015
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AGENDA • LOOKING FOR A BIOMARKER • CLUES IN THE CLINICAL SETTING • BEYOND THE CLINICAL PERSPECTIVE
Clinically Meaningful Outcomes in Clinical Trials in Cancer: an ASCO Cancer Research Committee Initiative <br />Ellis, et al., JCO 32:1277, 2014 Presented By Lowell Schnipper at 2015 ASCO Annual Meeting
Slide 20 Presented By Lowell Schnipper at 2015 ASCO Annual Meeting
Slide 10 Presented By Elisabeth De Vries at 2015 ASCO Annual Meeting
Immune Checkpoint Therapy: What Is Next? Anti–PD-1/PD-L1 Your favorite treatment The future of cancer therapy
Sex ♀/♂ Age > 18 PDL1+ (strong) Smoker KRAS mut Steroid free Director (CEO) > 200000 €/y