Neues aus der Onkologie Jörg Thomalla

Transkript

1 Neues aus der Onkologie 2015 Was haben neue Wirkstoffe gebracht? Jörg Thomalla

2 Wirkstoffe mit gleicher Indikationstellung und gleichem Wirkmechanismus Beispiel malignes Melanom Kombination BRAF-Inhibitor + MEK-Inhibitor Vemurafenib + Cobimetinib Dabrafenib + Trametinib Anti-PD1-Antikörper Nivolumab Pembrolizumab Wirksamkeit Nebenwirkungsprofil Differenzialindikation Therapiesequenz

3 Wirkstoffe mit gleicher Indikationstellung und unterschiedlichem Wirkmechanismus Beispiel malignes Melanom mit BRAF-Mutation Kombination BRAF-Inhibitor + MEK-Inhibitor Anti-PD1-Antikörper Anti-CTLA4-Antikörper Wirksamkeit Nebenwirkungsprofil Differenzialindikation Therapiesequenz

4 Wirkstoffe für Therapiesequenzen Beispiel Lungenkarzinom mit EML-ALK-Translokation Crizotinib Ceritinib

5 Beispiele: Arzneimittel für molekular charakterisierte Tumorleiden Molekulargenetische Diagnostik Mammakarzinom Hormonrezeptoren, Her2 Melanom BRAF Ovarialkarzinom BRCA1/2-Mutation ABER Für die meisten Wirkstoffe gibt es keine prädiktiven Biomarker

6 Neue Wirkmechanismen Tumorzelle DNA-Reparatur: PARP-Inhibitoren DNA-Transkription: Histon-Deacetylase-Inhibitoren Immun-Regulation (Check-Point-Inhibitoren) PD1-Antikörper PDL1-Antikörper

7 Histon-Deacetylase-Inhibitor (HDAC)

8

9 Neuartige Wirkmechanismen = Neue unerwünschte Effekte

10 Gezielte Therapie FIKTION oder REALITÄT? Vielfältige unerwünschte Effekte

11 Neue unerwünschte Effekte Leukozytose (Ibrutinib) QT-Verlängerung (Lenvatinib, Ceritinib) Herzrhythmusstörungen (Panobinostat) Autoimmunerkrankungen (Nivo, Pembro) Myelodysplasie (Olaparib)

12 CAVE Arzneimittelinteraktionen Beispiele Ibrutinib Marcumar QT-Verlängerung

13 Überblick 2015 Monoklonale Antikörper Antiangiogenese Ramucirumab (Cyramza ) -> VEGFR-2 Immun-Checkpunkt-Inhibitoren Nivolumab (Opdivo ) -> PD1 Pembrolizumab (Keytruda ) -> PD1 Kleinmolekulare Wirkstoffe Enzyminhibitoren Proteinkinaseinhibitoren Lenvatinib (Lenvima ) -> VEGFR1-3, PDGFRa, FGFR1-4, KIT, RET Nintedanib (Vargatef ) -> VEGFR1-3, PDGFRa, FGFR1-3 Ceritinib (Zykadia ) -> ALK Ibrutinib (Imbruvica ) -> Bruton-Tyrosin-Kinase Trametinib (Mekinist) -> MEK PARP-Inhibitoren Olaparib (Lynparza ) HDAC-Inhibitoren Panobinostat (Farydak )

14

15

16

17

18

19

20

21 Olaparib Nebenwirkungen Übelkeit, Erbrechen Diarrhoe Oberbauchschmerzen Asthenie Kopfschmerzen Hämatologische Toxizität Myelodysplasie / AML Pneumonitis

22 Immun Checkpoint - Inhibitoren Anti-PD-1 Antikörper Anti-PDL-1-Antikörper

23 Slide 3 Presented By Suzanne Topalian at 2015 ASCO Annual Meeting

24 Slide 4 Presented By Suzanne Topalian at 2015 ASCO Annual Meeting

25 Slide 8 Presented By Suzanne Topalian at 2015 ASCO Annual Meeting

26 Slide 9 Presented By Suzanne Topalian at 2015 ASCO Annual Meeting

27 Slide 10 Presented By Suzanne Topalian at 2015 ASCO Annual Meeting

28 Immun Checkpoint - Inhibitoren Anti-PD-1 Antikörper Opdivo (INN:Nivolumab) Keytruda (INN:Pembrolizumab)

29 Efficacy and Safety Results From a Phase III Trial of Nivolumab Alone or Combined With Ipilimumab vs. Ipilimumab Alone in Treatment-naïve Patients With Advanced Melanoma (CheckMate 067) Presented By Jedd Wolchok at 2015 ASCO Annual Meeting

30 Slide 6 Presented By Jedd Wolchok at 2015 ASCO Annual Meeting

31 Slide 10 Presented By Jedd Wolchok at 2015 ASCO Annual Meeting

32 Slide 16 Presented By Jedd Wolchok at 2015 ASCO Annual Meeting

33 Principal Take Home Message Presented By Michael Atkins at 2015 ASCO Annual Meeting

34 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

35 CheckMate 017 (NCT ) - Study Design Presented By David Spigel at 2015 ASCO Annual Meeting

36 Overall Survival Presented By David Spigel at 2015 ASCO Annual Meeting

37 Progression-Free Survival Presented By David Spigel at 2015 ASCO Annual Meeting

38 Response Characteristics of Confirmed Responders Presented By David Spigel at 2015 ASCO Annual Meeting

39 Summary Presented By David Spigel at 2015 ASCO Annual Meeting

40 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

41 The New Standard of Care <br />for the Treatment of Previously Treated Non-Squamous Cell Non-Small Cell Lung Cancer? Presented By Roy Herbst at 2015 ASCO Annual Meeting

42 CheckMate 057 (NCT ) Study Design Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

43 Objective Response Rate Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

44 Overall Survival Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

45 Progression-free Survival Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

46 Treatment-related AEs Reported <br />in 10% of Patients Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

47 Summary Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

48 Time s up!<br />Conclusions<br /> Presented By Roy Herbst at 2015 ASCO Annual Meeting

49 Slide 27 Presented By Suzanne Topalian at 2015 ASCO Annual Meeting

50 Neue Wirkstoffe 2015 Tumorentitäten Magenkarzinom Ramucirumab Melanom Nivolumab Pembrolizumab Trametinib Lungenkarzinom Nintedanib Nivolumab Schilddrüsenkarzinom Lenvatinib Ovarialkarzinom Olaparib Lymphome Ibrutinib

51 Die Verlierer Pankreaskarzinom Glioblastom Kolorektales Karzinom Mammakarzinom (triple negativ)

52 ENDE