Targeterbare mutationer / biomarkører Status og udfordringer for patologien

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1 Targeterbare mutationer / biomarkører Status og udfordringer for patologien Birgit Guldhammer Skov overlæge, dr.med. Patologi afdelingen Rigshospitalet

2 Biomarkers lung cancer Last 3-5 years More and more personalized medicin Specific pathways more details about the tumor

3 Gefitinib Erlotinib Afatinib Crizotinib Ceretinib

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5 DK RegH 1256 consecutive patients with NSCLC 8 % ACL (58% never smokers) 1.87 % SQC (0 never smokers) EGFR mutated 89% activating mutations

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7 Status i Danmark for EGFR testning ved lunge cancer: vi følger internationale guidelines: (Alle?) patienter med Adenocarcinom/non-Squamous cell karcinom testes up front Test: PCR baseret analyse Svar: inden for 1 uge Afventer data fra DLCR for kompletheds grad

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11 DK RegH 797 consecutive patients with ACL-3.0) all with 3+ reaction 14 patients = 1.8% (95% CI ) with Alk translocation

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13 Status i Danmark for ALK testning ved lunge cancer: vi følger internationale guidelines: (Alle?) patienter med Adenocarcinom testes En del testes up front Test: IHC baseret analyse, konfirmeres med FISH Afventer data fra DLCR for kompletheds grad

14 Mutation depending on the ALK inhibitor

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21 Summary EGFR and ALK mutation-positive pulmonary adenocarcinoma is a continually evolving disease Rebiopsy can help identify mechanisms of resistance to EGFR-TKI and ALK-TKI Third generations EGFR-TKI are effective in T790Mpositive tumors Second and third generations ALK-TKI are effective in some crizotinib resistance tumors Approximately 10 (15)% of danish patients with pumnonary adenocarcinoma habour an mutation that can be treated by targeted therapy

22 Titel/beskrivelse (Sidehoved/fod) 22 Navn (Sidehoved/fod)

23 Biomarkers lung cancer Last few years last 3-5 years More and more personalized medicine Specific pathways more details about the tumor Now Focus on the immune system. Is the tumor protected by the immunesystem?

24 Stimulere kroppens eget immun forsvar til at bekæmpe tumor Fjerne hæmning af immunrespons i tumor miljø

25 A Phase III Study (CheckMate 017) <br />of Nivolumab (Anti-Programmed Death-1) <br />vs Docetaxel in Previously Treated Advanced or Metastatic Squamous (SQ) Cell Non-Small-Cell Lung Cancer (NSCLC) Presented By David Spigel at 2015 ASCO Annual Meeting

26 10/14/

27 FDA News Release March 4, 2015 The U.S. Food and Drug Administration today expanded the approved use of Opdivo (nivolumab) to treat patients with advanced (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

28 Phase III, Randomized Trial (CheckMate 057)<br />of Nivolumab versus Docetaxel <br />in Advanced Non-squamous (non-sq) Cell Non-small Cell Lung Cancer (NSCLC) Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

29 OS and PFS Hazard Ratios by Baseline PD-L1 Expression Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

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32 FDA Approves KEYTRUDA (pembrolizumab) for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer Whose Tumors Express PD-L1 with Disease Progression On or After Platinum-Containing Chemotherapy Friday, October 2, :49 pm EDT Approval of PD-L1 Companion Diagnostic for Patients with Advanced NSCLC In parallel with the approval of KEYTRUDA, the FDA has also given Pre-Market Approval (PMA) to the first predictive companion diagnostic for use in detecting PD-L1, an immune-related biomarker expressed on some tumor cells: the PD-L1 IHC 22C3 pharmdx kit made by Dako North America, Inc., an Agilent Technologies Company.

33 Garon EB et al. N Engl J Med 2015;372: PD-L1 ExprFigure 1. PD-L1 Expression in Non Small-Cell Lung Cancers

34 <br /> Efficacy, safety and predictive biomarker results from a randomized Phase II study comparing atezolizumab (MPDL3280A) vs docetaxel in 2L/3L NSCLC (POPLAR) Presented By Alexander Spira at 2015 ASCO Annual Meeting

35 Rigshospitalet

36 PD-L1 Expression on TC and IC is a Potential Predictive Biomarker for Atezolizumab in NSCLC Presented By Alexander Spira at 2015 ASCO Annual Meeting

37 Titel/beskrivelse (Sidehoved/fod) Navn (Sidehoved/fod) 37

38 Titel/beskrivelse (Sidehoved/fod) 38

39 Rigshospitalet Udfordringer med PDL-1 som biomarkør (1) Forskellige PDL1 antistoffer Forskellige platforme Forskellig definition på positiv Skal vi kun evaluere på tumorceller? Hvad med TIL s? Hvad med den invasive front? Hvornår og på hvilket materiale skal analysen laves ( dynamisk markør )? Kan vi bruge cytologisk materiale?????? 10/14/