Neue Onkologika. Markus Joerger MD PhD ClinPharm. Department of Medical Oncology Cantonal Hospital St.Gallen Switzerland

Transkript

1 Neue Onkologika Markus Joerger MD PhD ClinPharm Department of Medical Oncology Cantonal Hospital St.Gallen Switzerland 1

2 Übersicht MammaCA: Pertuzumab (Perjeta ), T DM1 (Kadcyla ) ProstataCA: Enzalutamide (Xtandi ), Abiraterone (Zytiga ), Radium 223 (Xofigo ) BronchialCA: Afatinib (Giotrif ) BasalzellCA: Vismodegib (Erivedge ) PancreasCA: Nab Paclitaxel (Abraxane ) Melanom: Vemurafenib Cobimetinib, Dabrafenib Trametinib Hämatologische Malignome (Lymphome, CLL): Obinutuzumab (Gazyvaro ), Ofatumumab (Arzerra ), Ibrutinib (Imbruvica ), Idelalisib (Zydelig ) 2

3 MammaCA T DM1 EMILIA Studie 3

4 4

5 MammaCA Pertuzumab CLEOPATRA Studie 5

6 Bronchialkarzinom Afatinib 6

7 Bronchialkarzinom Afatinib (LUX 3) 1269 screened, 452 EGFR mutation (+) => 345 randomized Sequist et al, J Clin Oncol Sep 20;31(27):

8 Bronchialkarzinom Afatinib (LUX 3) 8

9

10

11

12 12

13 13

14 Vismodegib BasalzellCA ERIVANCE Studie (P2) Metastatic BCC (RECIST measurable) Locally advanced BCC REGISTRATION RECIST Vismodegib Composite endpoint Progression Intolerable toxicity Withdrawal from study Locally advanced BCC: Inoperable Surgery inappropriate 1 cm 2 recurrences after surgery and curative resection unlikely and/or anticipated substantial morbidity and/or deformity from surgery RECIST, Response Evaluation Criteria In Solid Tumors 14

15 Vismodegib BasalzellCA ERIVANCE Studie (P2) Parameter mbcc (n=33) labcc (n=63) Overall Response Rate (ORR) 30% 43% Median Duration of Response (DOR), months Median Progression Free Survival (PFS), months Baseline Week 8 Week 20 Sekulic et al, New Engl J Med, 366(23): ;

16 16

17 17

18 BRAF 600E Melanoma PDGFRb or IGF1R Nazarian et al. Nature 2010 NRAS Q61 BRAF inh PI3K Nazarian et al. Nature 2010 Villanueva et al. Cancer Cell 2010 Johannessen et al. Nature 2010 COT MEK-dependent progression CRAF BRAF V600E P P MEK MEKi ERK Poulikakos et al. Nature 2011 Wagle et al. JCO 2011 PI3Ki or AKTi AKT MEK-independent progression Survival 18

19 Vemurafenib/Dabrafenib RAS o pathy 19

20 Combined BRAF MEK Inhibition Toxicity Flaherty et al. N Engl J Med Nov;367(18):

21 Vemurafenib Cobimetinib CoBrim Studie 21

22 Dabrafenib Trametinib Combi v Studie

23 23

24 Obinutuzumab (GA101) anti CD20 mab CLL 24

25 Obinutuzumab (GA101) anti CD20 mab CLL 25

26 Ofatumumab anti CD20 mab CLL Study design: Multinational, open label, single arm study: in 154 patients with fludarabine refractory CLL Cohort A: double refractory to both fludarabine and alemtuzumab (n=59) Cohort B: refractory to fludarabine and inappropriate for alemtuzumab due to bulky lymph nodes (>5 cm) (n=79) 26

27 Ibrutinib Bruton Tyrosinkinase Inhibitor MCL 27

28 Idelalisib PI3K Inhibitor CLL

29 Neue Onkologika Schlusswort Molekulares Targeting > Akzeleration von Neuzulassungen Anspruchsvoll bzgl. Einsatz/Verordnung, Anwendung, Patientenaufklärung, Nebenwirkungs Management Zunehmende Heterogenität der Zulassungen per Land Zunehmend off label Verwendung von Onkologika Kostenfolgen 29

30