Målstyrd behandling vid lungcancer Karl-Gustaf Kölbeck, öl, sektionschef Lung Allergikliniken Karolinska Universitetssjukhuset

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1 Rapport från ASCO- Och kliniken Målstyrd behandling vid lungcancer Karl-Gustaf Kölbeck, öl, sektionschef Lung Allergikliniken Karolinska Universitetssjukhuset

2 Vad är målstyrd behandling vid cancer? drugs or other substances that interfere with specific molecules involved in cancer cell growth and survival. Traditional chemotherapy drugs, by contrast, act against all actively dividing cells NCI,

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4 Evolution of Identification of Genomic Alterations in Lung Adenocarcinoma Presented By Pasi Janne at 2014 ASCO Annual Meeting

5 Management and Future Directions in NSCLC with Known Activating Mutations Presented By Daniel Costa at 2014 ASCO Annual Meeting

6 EGFR-muterad lungcancer: Kliniska karakteristika Oberoende av rökstatus (?) Drabbar alla åldrar (>30) Prognostisk betydelse: Fördubblad medianöverlevnad jämfört annan lungcancer Prediktiv betydelse: Svarar bra på både målstyrd behandling och traditionell cytostatikabehandling Titta noggrant på svar från lab: Vilken typ/typer av mutationer? 6

7 EGFR mutations in NSCLC cluster around the tyrosine kinase domain (ATP binding pocket) of EGFR (2) Presented By Daniel Costa at 2014 ASCO Annual Meeting

8 Different EGFR mutated NSCLCs and EGFR TKIs<br />(different therapeutic windows in relation to EGFR WT) Presented By Daniel Costa at 2014 ASCO Annual Meeting

9 Background: afatinib Presented By James Yang at 2014 ASCO Annual Meeting

10 Afatinib: Överlevnadsdata från Lux Lung 3 och 6 Combined OS analysis: mutation categories Presented By James Yang at 2014 ASCO Annual Meeting

11 Is OS with Afatinib in LUX-Lung 3/6 Superior to That of Other EGFR TKIs? Presented By Howard West at 2014 ASCO Annual Meeting

12 Could Low Crossover <br />Explain the Difference? Presented By Howard West at 2014 ASCO Annual Meeting

13 Relevant Comparison for Afatinib<br />in 2014 is to Other EGFR TKIs Presented By Howard West at 2014 ASCO Annual Meeting

14 EGFR TKIs and EGFR mutated NSCLC:<br />major mechanisms of resistance to EGFR TKIs (2) Presented By Daniel Costa at 2014 ASCO Annual Meeting

15 Vad göra vid progress? (Evidensbaserade råd finns ej) Asymtomatisk (långsam) progress: fortsätt med insatt TKI. Planera gärna in re-biopsi! Progress i en metastas: Riktad behandling (ex.srt hjärna, binjure), fortsätt insatt TKI Symtomgivande progress: Traditionell cytostatikabehandling. Om förutsättningar finns först re-biopsi: #T790M påvisad: 1:a-2:a generationens TKI dålig effekt. Studie. #Met-amplifiering: Krizotinib? #Transformering till småcellig lungcancer: Kemo Costa, ASCO

16 Therapies for acquired resistance to EGFR TKIs in <br />EGFR mutated NSCLC (covalent EGFR-T790M AZD9291) Presented By Daniel Costa at 2014 ASCO Annual Meeting

17 Tumor Shrinkage Seen in Intermediate <br />and High MET Cohorts Presented By D. Camidge at 2014 ASCO Annual Meeting

18 Obesvarade frågor om EGFR-muterad lungcancer (Costa, ASCO 2014) Vilken roll har EGFR-TKI:s vid stadium l-lll? Vilken TKI (gefitinib/erlotinib/afatinib) skall användas för EGFR L858R repektive exon 19 deletion, samt för mindre vanliga mutationer? Vilken plats har fortsatt terapi med initial TKI vid sjukdomsprogression? Vilken tredje generationens TKI skall användas vid T790M mutation? Hur mycket dokumentation/studier behövs innan registrering? Vilka behandlingskombinationer kan försena eller förhindra behandlingsresistens vid EGFR-positiv lungcancer? Karl Kölbeck Lungcancerbehandling jan

19 Erlotinib plus bevacizumab versus <br />erlotinib alone as first-line treatment for advanced EGFR mutation-positive<br />non-squamous non-small-cell lung cancer: <br />an openlabel, randomized trial Presented By Terufumi Kato at 2014 ASCO Annual Meeting

20 Study design Presented By Terufumi Kato at 2014 ASCO Annual Meeting

21 EGFR Regulates VEGF in <br />EGFR Mutant Cell Lines Presented By Howard West at 2014 ASCO Annual Meeting

22 PFS by EGFR mutation type Presented By Terufumi Kato at 2014 ASCO Annual Meeting

23 Cost Considerations with <br />Erlotinib/Bev Combination Presented By Howard West at 2014 ASCO Annual Meeting

24 JO25587 PFS in Context of Other Trials<br />in EGFR Mutation-Positive NSCLC Presented By Howard West at 2014 ASCO Annual Meeting

25 ALK-rearrangerad lungcancer: Företrädelsevis adenocarcinom Ofta yngre individer Aldrig rökare eller nästan 4% av all lungcancer Karl Kölbeck Lungcancerbehandling jan

26 Slide 20 Presented By Leena Gandhi at 2014 ASCO Annual Meeting

27 Slide 10 Presented By Leena Gandhi at 2014 ASCO Annual Meeting

28 <br />Crizotinib: selective inhibitor of <br />ALK, MET and ROS Presented By D. Camidge at 2014 ASCO Annual Meeting

29 ASCEND 1: Ceritinib vid ALK+ NSCLC Progression-Free Survival in Patients with ALK+ NSCLC Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting

30 Overall Response Rate in ALK+ NSCLC Patients Treated with Ceritinib (750 mg daily) Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting

31 Overall Intracranial Response Rate for Patients with Measurable Brain Metastases at Baseline Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting

32 Målstyrd behandling vid NSCLC Inregistrerade läkemedel för lungcancer: Mekanism Indikation generiskt namn handelsnamn EGFR-TKI EGFR-muterad lungcancer gefitinib, erlotinib, afatinib Iressa, Tarceva, Giotrif ALK-rubbning ALK-rubbad lungcancer 2:a linjen krizotinib Xalkori Tillgängligt läkemedel för annan mekanism: Mekanism Indikation generiskt namn handelsnamn ROS-1 mutation 2:a linjen lungcancer krizotinib Xalkori Met-amplifiering? krizotinib Xalkori HER-2 mutation? afatinib Giotrif BRAF V600-mutation? vemurafenib Zelboraf RET-mutationspositiv? vandetanib Caprelsa Karl Kölbeck Lungcancerbehandling jan

33 Tack! Karl Kölbeck Lungcancerbehandling jan