NSCLC (TEIL 1) IMMUNONKOLOGIE (I-O) MITTELS CHECKPOINT- INHIBITION: REVOLUTION DER NSCLC-THERAPIE?

NSCLC (TEIL 1) IMMUNONKOLOGIE (I-O) MITTELS CHECKPOINTINHIBITION: REVOLUTION DER NSCLC-THERAPIE? Wichtige Mediatoren der Immunabwehr Angeboren Antig...
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NSCLC (TEIL 1) IMMUNONKOLOGIE (I-O) MITTELS CHECKPOINTINHIBITION: REVOLUTION DER NSCLC-THERAPIE?

Wichtige Mediatoren der Immunabwehr Angeboren Antigen unabhängig Antigenpräsentierende Zellen

DC

Adaptiv Antigen abhängig

Lymphokine

TLR* PRR*

NKG2D

IL´e IFN´e CK´e ...

Adaptiert nach Woelfel et al, 2014

KIR

T-Zellen

Fc

„natürliche Killer-Zellen“

NK

B-Zellen

Fab

T

Fab

CTLA-4

CD28

TCR IFN-g Perforin Granzym B

Wichtige Mediatoren der Immunabwehr Angeboren Antigen unabhängig Antigenpräsentierende Zellen

DC

Adaptiv Antigen abhängig

Lymphokine

TLR* PRR*

NKG2D

IL´e IFN´e CK´e ...

Adaptiert nach Woelfel et al, 2014

KIR

T-Zellen

Fc

„natürliche Killer-Zellen“

NK

B-Zellen

Fab

T

Fab

Anpassungsfähigkeit Spezifität CTLA-4 Gedächtnis

CD28

TCR IFN-g Perforin Granzym B

Die T-Zell-vermittelte antitumorale Immunantwort 2

1

Präsentation von Tumorantigen gegenüber der T-Zelle

Tumor: Freisetzung von Tumorantigenen

3

4

Erkennung von Tumorantigen durch T-Zellen

5

Zerstörung des Tumors durch T-Zellen

Andersen et al, J Invest Dermatol 2006, 126: 32; Pardoll DM, Nat Rev Cancer 2012, 11: 252; Mellman et al, Nature 2011, 480: 480; Heemskerk et al, EMBO J 2013, 32: 194; Boudreau et al, Mol Ther 2011, 19: 841; Janeway et al, Immunobiology: The Immune System in Health and Disease. 6th ed, 2004.

T-Zell-Aktivierung und Proliferation

Immunsystem und Krebs: Der Prozess des Immunoediting Die drei “E” des Immunoediting beschreiben die Prozesse der Tumorkontrolle durch das Immunsystem und wie der Tumor dieser Kontrolle entkommt.

Elimination Tumor-Immunüberwachung

CD8+ T-Zelle

CD4+ T-Zelle

Equilibrium

Escape

Tumor-Ruhezustand (“Survival of the fittest”)

Tumor-Wachstum

NK Zelle Treg Tumorzellen

Normale Zellen

Vesely et al, Ann Rev Immunol 2011, 29: 235

Immune Escape-Mechanismen: Tumore nutzen komplexe Mechanismen, dem Immunsystem zu entkommen A. Ineffektive Tumor-AntigenPräsentation (gp100, MART-1, verringerte MHC-Expression)

CD8+ TZelle

TCR

VEGF APC

B. Rekrutierung immunsuppressiver Zellen (regulatorische T-Zellen =Tregs, MDSCs, andere)

MHC

CTLA-4 MDSC

Treg

PD-L1

Tumorzellen

PD-1 PD-L1 PD-1 TGF-β IDO IL-10

TGF-β ARG1 iNOS

TGF-β IL-10

CD4+

D. T-Zell-Checkpoints

Vesely et al, Ann Rev Immunol 2011, 29: 235

TZelle

CD8+ TZelle

C. Sekretion von immunsuppressiven Signalen (z.B. PD-L1, TGF-β, IL-10, und indolamine 2,3dioxygenase [IDO])

Die Immunonkologie mittels Checkpoint-Modifikation als neues therapeutisches Behandlungskonzept1 •



Die konventionellen onkologischen Ansätze sind direkt gegen den Tumor gerichtet.2 Bei der Immunonkologie wird die natürliche Fähigkeit des eigenen Immunsystems genutzt, um den Krebs zu bekämpfen.2

Operation

Immunonkologie

Strahlentherapie

Chemo- & zielgerichtete Therapien

1. DeVita and Rosenberg, N Eng J Med 2012, 366: 2207; 2. Borghaei et al, Eur J Pharmacol 2009, 625: 41.

Regulation der T-Zell-Aktivität: Checkpoint-Moleküle Aktivierende Rezeptoren

Inhibierende Rezeptoren

CTLA-4

CD28

PD-1 OX40 TIM-3 CD137

LAG-3

Aktivierung Immunsystem Adapted from Mellman I, et al. Nature. 2011:480;481–489; Pardoll DM. Nat Rev Cancer. 2012;12:252–264.

Neues Therapeutisches Konzept: Blockade der CTLA-4- und PD-1-Checkpoint-Signalwege Mikroumgebung des Tumors

Lymphknoten

Aktivierung (Zytokine, Lyse, Proliferation, Migration zum Tumor) MHC

TCR

TCR

Dendritische B7 CD28 Zelle B7 CTLA-4

+++

+++ +++ T-Zelle ---

Anti-CTLA-4

MHC

T-Zelle

PD-1

PD-L1

---

Tumorzelle

Anti-PD-1/PD-L1 PD-1

PD-L2

--Anti-PD-1

CTLA-4-Signalweg CTLA-4 reguliert die Amplitude der frühen Aktivierung von naiven und Memory T-Zellen.

Wolchock et al, J Clin Oncol 2013 ASCO Annual Meeting Abstracts 31:15_suppl

PD-1-Signalweg PD-1 begrenzt die T-Zell-Aktivierung in der Peripherie während einer Entzündungsreaktion.

Die Immunonkologie: Proof of Concept Langzeitdaten Ipilimumab von 1.861 Melanompatienten (8 Ph. II-, 2 Ph. III-, 2 Ph. IV-Studien) Wahrscheinlichkeit Gesamtüberleben



1.0 0.9 0.8 0.7

Medianes OS, Monate (95% KI): 11,4 (10,7–12,1) 3-Jahres OS-Rate, % (95% KI): 22 (20–24)

0.6 0.5 0.4 0.3 0.2 0.1

Ipilimumab Zensiert

0.0 0

12

24

36

48

60

72

84

96

108

120

120

26

15

5

0

Monate Patienten unter Progressionsrisiko Ipilimumab 1.861 839 370

254

192

170

Schadendorf et al, annual presentation at ECCO/ESMO 2013, abstract # 24LBA

Die Immunonkologie und „Hallmarks of Cancer“

Adapted from Hanahan et al, Cell 2011; 44: 646

Immuntherapeutische Ansätze am Beispiel Lungenkrebs Immuntherapie Passiv (adoptiv)

Aktiv

Zielt auf den Tumor; Immun-basierter Mechanismus

Zielt auf das Immunsystem direkt

Antigenabhängig

Antigenunabhängig

Verstärkt die Funktion der Immunzelle

Therapeutische Vakzine

Moduliert die TZell Funktion

Zytokine

GSK1572932A TG4010 Belagenpumatucel-L Tergenpumatucel-L Racotumomab Stimuvax CIMAvax

Antitumorale monoklonale Antikörper

Adoptiv

Bavituximab EGFR Inhibition

Adoptiver Zelltransfer

Immun-Onkologie (I-O) CTLA-4-Inhibition PD-1-Inhibition PD-L1-Inhibition

CTLA-4 = cytotoxic T-lymphocyte antigen-4; PD-1 = programmed death-1; PD-L1 = programmed death ligand-1 www.clinicaltrials.gov accessed 26 March 2014; NCCN Guidelines ®. NSCLC. V2.2013; Peters et al. Ann Oncol. 2012;23:vii56

Klinische Entwicklung: Immun-Checkpoint-Inhibitoren – PD-1-/PD-L1-Signalweg

Target

Antibody

a

Nivolumab (BMS-936558) PD-1

Pembrolizumab (MK-3475) Pidilizumab (CT-011) MEDI-4736

PD-L1

MPDL3280A MSB0010718C

Development Stage Phase 1-3: multiple tumors (melanoma, RCC, NSCLC, HNSCC, GBM, Hodgkin, others) Phase 1/2: multiple tumors Phase 3: NSCLC Approved: melanoma Phase 1/2: multiple tumors Phase 1/2: multiple tumors Phase 2: CRC, HNSCC Phase 3: NSCLC Phase 1/2: multiple tumors Phase 2: RCC, bladder Phase 3: NSCLC Phase 1/2: multiple tumors

CRC = colorectal cancer; GBM = glioblastoma multiforme; HNSCC = head and neck squamous cell carcinoma; RCC = renal cell carcinoma a List incomplete www.clinicaltrials.gov. Accessed March 25, 2015.

Phase I-Studie Nivolumab Monotherapie: Design der NSCLC-Kohorte (CA209-003) • Phase 1 study of the safety, antitumor activity, and pharmacodynamics of nivolumab in patients with advanced solid tumors1 • Nivolumab 0,1 to 10 mg/kg Q2W for a maximum of twelve 8-week treatment cycles (2 years); expansion cohorts for select tumor types2 • 1–5 previous therapies1 • In the 129 patients with NSCLC – 42% had squamous and 57% had non-squamous histology – 54% received ≥3 prior therapies2

IV = intravenous; Q2W = every 2 weeks. 1. Topalian SL, et al. N Engl J Med. 2012;366:2443-2454. 2. Brahmer JR, et al. Presented at ASCO 2013. Abstract 8030.

Nivolumab 1 mg/kg IV Q2W (n=33)

Eligible patients with NSCLC randomized between 3 nivolumab dose levels

Nivolumab 3 mg/kg IV Q2W (n=37)

(n=129) Nivolumab 10 mg/kg IV Q2W (n=59)

Der anti-PD-1-AK Nivolumab bei fortgeschrittenen Tumorerkrankungen: Phase I – CA209-003

Tumor Type NSCLC Squamous Nonsquamous MEL RCC

ORR n/N (%) [95% CI] 22/129 (17,1) [11,0, 24,7] 9/54 (16,7) [17,9, 29,3]

Median Duration of Response, wk (range) 74,0 (6,1+, 133,9+) NR (16,1, 133,9+)

Stable Disease, n/N (%) [95% CI] ≥ 24 wk 13/129 (10,1) [5,5, 16,6] 8/54 (14,8) [6,6, 27,1]

Median PFS, mo [95% CI] 2,3 [1,9, 3,7] 3,7 [1,8, 7,2]

13/74 (17,6) [9,7, 28,2]

63,9 (6,1+, 74,0+)

5/74 (6,8) [2,2, 15,1]

2,0 [1,8, 3,6]

33/107 (30,8) [22,3, 40,5] 10/34 (29,4) [15,1, 47,5]

104,0 (18,4, 117,0+) 56,1 (36,6, 126,7+)

7/107 (6,5) [2,7, 13,0] 9/34 (126,5) [12,9, 44,4]

3,7 [1,9, 9,1] 7,3 [3,7, 12,9]

Hodi et al, Poster presentation at ECC 2013:abstract 880

Nivolumab beim fortgeschrittenen NSCLC: Überleben Phase I CA209-003 (mehrfach vorbehandelte Patienten) 100

OS rate, % (95% CI)

90

Censored

80 70

Group

Died/Treated

1 mg/kg 3 mg/kg 10 mg/kg

99/129 23/37 50/59

Median OS, mo (95% CI) 9,9 (7,8, 12,4) 14,9 (7,3,30,3) 9,2 (5,2,12,4)

1 Year

2 Years

3 Years

42 (33, 50) 56 (38,71) 38 (26, 50)

24 (17, 33) 42 (24,58) 20 (11, 31)

18 (11, 25) 27 (12, 43) 14 (7, 25)

OS (%)

60 50

2-year OS = 42%

40

3-year OS = 27%

30 20 10 0 0

3

6

9

12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66

Months Since Initiation of Treatment

Pts at Risk Nivolumab 1 mg/kg

33

26

21

16

9

7

6

6

4

4

4

3

1

1

0

0

0

0

0

0

0

0

0

Nivolumab 3 mg/kg

37

34

26

21

17

14

13

12

11

9

9

7

5

2

1

1

1

1

1

1

1

1

0

Nivolumab 10 mg/kg

59

51

35

29

22

16

14

12

11

10

9

9

6

4

2

2

2

1

1

0

0

0

0

Gettinger et al, CMSTO 2014

Der anti-PD-1-AK Pembrolizumab beim fortgeschrittenen NSCLC: Phase I-Studie – Wirksamkeit RECIST v1.1, Independent Review

irRC, Investigator Review Subgroup

n

ORR, n (%) [95% CI]

Median PFS, wk (95% CI)

n

ORR,* (%), [95% CI]

Median PFS, wk (95% CI)

Median OS, wk (95% CI)

All

38

9 (24%) [11%, 40%]

9,1 (8,3, 17,4)

33

7 (21%) [9%, 39%]

9,7 (7,6, 17)

51 (14, NR)

Non-squamous

31

7 (23%) [10%, 41%]

9,1 (8,3, 17,0)

26

4 (16%) [4%, 35%]

10,3 (7,6, 17)

35 (14, NR)

Squamous

6

2 (33%) [4%, 78%]

23,5 (2,7, NR)

6

2 (33%) [4%, 78%]

15,2 (1,4, NR)

NR (2,7, NR)

Patients with measurable disease on baseline imaging and an evaluable tumor specimen for PD-L1 Score ≥ potential cut point

9

6 (67%) [30%, 93%]



7

4 (57%) [18%, 90%]





Score < potential cut point

24

1 (4%) [0%, 21%]



22

2 (9%) [1%, 29%]





Garon et al, WCLC 2013, #2416

Einfluss der Histologie – Wirksamkeit der Anti-PD-1-/PD-L1-Antikörper Nivolumab

MPDL3280A

Squamous

NS

S NS NS NS S

Nonsquamous

NS

On study, on treatment

S

0

16

32

48

64

80

96

Time (week)

On study, post treatment

Duration of response on study

NS

Treatment discontinued

Ongoing response

NS

Ongoing response

Time to response

NS

First response

Response duration after discontinuation

NS

First PD

112

128

144

160

0

6

12

18

24

30

36 42

48

Time (weeks)

Adapted from Brahmer JR, et al. Mini-Oral presentation at WCLC 2013. J Thorac Oncol. 2013;8(Suppl 2):abstract: MO18.03; Horn L, et al. Mini-Oral presentation at WCLC 2013. J Thorac Oncol. 2013;8(Suppl 2):abstract: MO18.01.

54

60

66

72

78

KEYNOTE-001: Geschätzte Überlebenskurve (Kaplan-Meier) PFS (Recist v1.1, Central Review)

• Treatment naive – Median PFS: 27 weeks (95% CI, 14–45) – 24-week PFS: 51% • Previously treated – Median PFS: 10 weeks (9,1–15,3) – 24-week PFS: 26%

Analysis cutoff date: March 3, 2014 Garon et al, Oral presentation at ESMO 2014

OS

• Treatment naive – Median OS: NR (95% CI, NE-NE) – 6-month OS: 86% • Previously treated – Median OS: 8,2 months (7,3 - NR) – 6-month OS: 59%

Klinisches Ansprechen nach PD-L1-Immunohistochemie Anti PD-1 MK-3475 ORR n/N (%) All patients

21%

Anti PD-L1 Nivolumab ORR n/N (%)

22/129 (17,1%)

MEDI4736 ORR n/N (%)

MPDL3280A ORR n/N (%)

9/58 (16%)

12/53 (23%)

PD-L1 Status (evaluable pts.) Positive

37/159 (23%)

5/31 (16%)

5/20 (25%)

8/26 (31%)

Negative

3/35 (9%)

4/32 (13%)

1/29 (3%)

4/20 (20%)

Offene Fragen • Unterschiedliche Gewebsentnahmezeiten • Unterschiedliche Antikörper und Assays • Unterschiedliche IHC-Kriterien

Horn L, J Thorac Oncol 2013; 8 (Suppl 2), #MO18.01; Brahmer JR, J Thorac Oncol 2013; 8 (Suppl2), #MO1803; Antonia SJ, J Thorac Oncol 2013 (Suppl 2), #P2 11-034; Garon E, ASCO 2014; #8020; Brahmer J, ASCO 2014, #8021

Pembrolizumab – Phase I-Studie

100 90 80 70 60 50 40 30 20 10 0

Strong Weak Negative

0 n at risk Strong Weak Negative

OS

8

16

24

32

40

Overall Survival, %

Progression-Free Survival, %

PFS (Recist v1.1, Central Review)

48

28 43 30

18 17 15

17 12 7

Strong Weak Negative 0

1

2

3

4

5

6

7

8

9 10 11 12 13 14

Time, months

Time, weeks 44 53 49

100 90 80 70 60 50 40 30 20 10 0

9 6 1

6 0 0

3 0 0

44 43 38 38 34 32 30 27 21 18 9 53 51 48 40 34 31 26 22 18 11 8 49 42 38 34 29 26 21 14 8 6 4

8 7 2

5 5 0

5 5 0

• PFS was longer in patients with PD-L1 strong-positive versus PD-L1 weak-positive/ negative tumors (HR, 0.52; 95% CI, 0.33-0.80) • OS was longer in patients with PD-L1 strong-positive versus PD-L1 weak-positive/ negative tumors (HR, 0.59; 95% CI, 0.35-0.99)

a Evaluable patients were those patients in the training set with evaluable tumor PD-L1 expression. Strong PD-L1 positivity defined as staining in ≥50% of tumor cells, and weak PD-L1 positivity as staining in 1-49% of tumor cells. Negative staining is no PD-L1 staining in tumor cells. Analysis cutoff date: March 3, 2014; Garon et al, Oral presentation at ESMO 2014

4 4 0

Korrelation zwischen PD-L1-Status und klinischem Outcome: Ein potentieller prädiktiver Biomarker?

Daten mit PD-1-Checkpoint-Inhibitoren weisen darauf hin, dass die PD-L1Expression im Tumor signifikant mit einem verbesserten Ansprechen und Überleben assoziiert ist1….. ABER

Patienten mit PD-L1-negativen Tumoren sprechen auch auf die Therapie an2,3…

1. Garon EB, et al. Presented at ESMO 2014. Abstract LBA 43. 2. Gettinger SN, et al. Presented at CMSTO 2014. Poster 170. 3. Ramalingam S, et al. Presented at CMSTO 2014. Abstract 3462

NSCLC – Zulassungsrelevante Studien mit Nivolumab STUDY

PRIMARY ENDPOINT

STATUS

PUBLICATION

Nivolumab

ORR

ongoing not recruiting

Rizvi N.A,, Wolf J., Grohé C., Huber R.M., et al. The Lancet Oncology 16.3 (2015): 257-265.

Allcomer

Nivolumab vs. Docetaxel

OS

ongoing not recruiting

2L+

Allcomer

Nivolumab vs. Docetaxel

OS

ongoing not recruiting

1L

PD-L1+

Nivolumab vs. ICC

PFS

ongoing not recruiting

LINE

ALLCOMER PD-L1+

PHASE

POPULATION

CA209-063

2

NSCLC squamous

3L+

Allcomer

CA209-017

3

NSCLC squamous

2L

CA209-057

3

NSCLC non-squamous

CA209-026

3

NSCLC squamous non-squamous

DESIGN

ORR = Objective Response Rate, OS = Overall Survival, PFS= Progression Free Survival, ICC = Investigator's Choice Chemotherapy www.clinicaltrials.gov

Nivolumab Phase II CA209-063: Studiendesign Population

Stage IIIB/IV NSCLC squamous • ≥2 prior systemic therapies • ECOG 0–1

Treatment

Endpoints Primary: • Confirmed ORR (IRC assessed)

Nivolumab 3 mg/kg IV Q2W* n=117

Secondary: • Confirmed ORR (investigator assessed) Exploratory: • Safety and tolerability • PFS/OS • PD-L1 expression and efficacy

Title: Study of Nivolumab (BMS-936558) in Subjects With Advanced or Metastatic Squamous Cell Non-Small Cell Lung Cancer Who Have Received At Least Two Prior Systemic Regimens (CheckMate 063)

ORR = Objective Response Rate, IRRC = Independent Radiology Review Committee OS = Overall Survival, PFS= Progression Free Survival * until disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends www.clinicaltrials.gov

CA209-063: Ansprechen und Überleben (Größte Reduktion der Targetläsion)a Best Reduction from Baseline in Target Lesion (%)

100

Alive Expired Confirmed responders

75 50 25 0 -25 -50 -75

n=95 response-evaluable

-100

Patient

• 8 confirmed PRs in patients with rapid progression on prior therapy • Among all treated patients; 13% continuing treatment and 24% received subsequent therapy – Most frequent therapies were gemcitabine (10%), docetaxel (4%), and vinorelbine (4%) – No patients received subsequent immunotherapy

a Based on July 2014 DBL; 22/117 treated patients are not displayed due to lack of evaluable on-study assessments; 18/22 expired; Dashed horizontal reference line indicates the 30% reduction consistent with a RECIST v1.1 response; Ramalingam et al. CMSTO 2014

CA209-063: Klinische Aktivität von Nivolumab Nivolumab 3 mg/kg ORR, % (n) [95% CI] Disease control rate, % (n) Median DOR, months (range)

IRC Assessed (per RECIST v1.1)a 15 (17) [9, 22] 40 (47) NR (2+, 12+)

Ongoing responders, % (n)

76 (13)

Median time to response, months (range)

3 (2, 9)

PFS rate at 1-year, % (95% CI)

20 (13, 29)

Median PFS, months (95% CI)

2 (2, 3)

• Investigator-assessed ORR was 13% (95% CI, 7, 20) – Concordance between IRC and investigator assessed responders was 92% (based on March 2014 DBL)

a July 2014 DBL NR = not reached; DOR = duration of response; ORR = objective response rate; PFS = progression free survival Ramalingam et al. CMSTO 2014

CA209-063: Ansprechmustera Percent Change in Baseline (%)

100

1st Occurrence of new lesion PR Patients still on treatment

75 50 25 0 -25 -50 -75 -100

0

6

12

18

25

30

36

42

48

54

60

Time Since First Treatment (Weeks)

• 4 patients with non-conventional responses not reported as IRC-assessed responders – 3 alive (OS: 12+, 13+, 14+ months)

a Based on July 2014 DBL Ramalingam et al. CMSTO 2014

66

CA209-063: Gesamtüberleben (OS): Alle behandelten Patientena

Overall Survival (%)

100

Median OS, months (95% CI)

8,2 (6, 11)

90

1-year OS rate, % (95% CI)

41 (32, 50)

80

Number of events

72/117

70

Median OS = 8,2 months

60 50

1-year OS = 41%

40 30 20 10 0 0

Number of Patients at Risk Nivolumab 117 3mg/kg



3

6

9

12

15

18

28

5

0

Overall Survival (Months) 93

68

51

Median follow-up for survival: 8 months (range 0–17 months)

a Based on July 2014 DBL; Symbols represent censored observations Ramalingam et al. CMSTO 2014

CA209-063: Therapiebedingte unerwünschte Ereignisse in ≥10% der Patientena Nivolumab 3 mg/kg (n = 117) Any Grade

Grade 3–4

74

17

Fatigue

33

4

Decreased appetite

19

0

Nausea

15

0

Asthenia

12

0

Rash

11

1

Diarrhea

10

3

Total patients with an event,b %

• • • •

85% of patients received at least 90% of their planned dose intensity 12% discontinued treatment due to study drug toxicity (4% pneumonitis) Grade 3 treatment-related pneumonitis was reported in 4 patients (3%); one additional grade 3 case occurred between 30–100 days after last nivolumab dose 62% had expired at time of analysis (54% PD and 2% study drug toxicity) – Two treatment-related deaths (1 hypoxic pneumonia and 1 ischemic stroke) occurred in patients with multiple comorbidities and concurrent PD

a July 2014 DBL; b Includes events reported between first dose and 30 days after last dose of study therapy. Of the adverse events included in the table, no events were grade 5 Ramalingam et al. CMSTO 2014

Studiendesign: CA209-017 und CA209-057

Phase 3 CA209-017

Stage IIIb/IV squamous cell NSCLC 2L

Phase 3 CA209-057

www.clinicaltrials.gov

Stage IIIb/IV nonsquamous cell NSCLC 2/3L

Nivolumab 3 mg/kg IV q2w

OS

Docetaxel 75 mg/m2 IV q3w

OS

Nivolumab 3 mg/kg IV q2w

OS

Docetaxel 75 mg/m2 IV q3w

OS

http://www.bms.com/news/press_releases/pages/default.aspx

Fazit: PD-1-Inhibition beim NSCLC •

Immun-Checkpoint-Inhibitoren zeigen ermutigende Ergebnisse in klinischen Studien (Phase 1-3)



Eindrucksvolles Ansprechen und Überleben bei vorbehandelten Patienten mit Adeno- und Plattenepithelkarzinomen



Ein Teil der Patienten zeigt möglicherweise ein Langzeitüberleben



Toxizität mäßig und beherrschbar



Mehrere Substanzen in klinischer Entwicklung



PD-L1 erster prädiktiver Biomarker, aber auch PD-L1-negative Patienten profitieren



Ausblick: Optimierung durch Kombinationstherapien

Die Immunonkologie als fest verankertes Behandlungskonzept in der Onkologie

Operation

Immunonkologie

Strahlentherapie

Chemo- & zielgerichtete Therapien

DeVita et al, N Eng J Med 2012; 366: 2207; Borghaei et al, Eur J Pharmacol 2009; 625: 41

Stand: April 2015 Bitte beachten Sie, dass sehr bald neue Daten und Updates der hier vorgestellten Studien folgen!