Behandling af lungekræft. Tine McCulloch onkologisk afdeling 5.februar 2013

Transkript

1 Behandling af lungekræft Tine McCulloch onkologisk afdeling 5.februar 2013

2 Lung Cancer 1st Page from Adler s Monograph published in 1912 Primary malignant growth of the lung Chapter I - From the Introduction: On one point, however, there is nearly complete Consensus of opinion and that is that primary Malignant neoplasms of the lung are among the rarest Forms of disease

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4 Lungecancerforløb i DLCR 2010: 4172 forløb Ålborg onkologisk afdeling 731 nyhenviste 15% SCLC 85% NSCLC

5 Lungekræft behandling i DK Dansk Lungecancer Register- registrering af behandling af lungekræft, årlige rapporter, kvalitetssikring Dansk Lungecancer Gruppe, multidisciplinær cancergruppe Dansk Onkologisk Lungecancer Gruppemedicinsk behandling af lungekræft og strålebehandling.

6 Småcellet lungekræft Hurtig vækst og metastasering. Ubehandlet er den gennemsnitlige overlevelse ca 2 mdr

7 SCLC Stadieinddeling Very limited disease (T1-2N0-1M0) udgør < 5% Limited disease begrænset sygdom kan omfattes af et strålefelt Extensive disease udvidet sygdom

8 SCLC Behandling VLD: OP og kemoterapi LD: kombination af kemo og strålebehandling. 5års overlevelse 20 % ED: kemoterapi, palliativ strålebehandling. Median overlevelse 10 mdr Profylaktisk cerebral bestråling.

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10 Udvikling siden 1960!

11 NSCLC - Stadieinddeling Lokal sygdom IA-IIIA(T3) ca 30% 5-årsoverlevelse ca 50% Lokalt avancerede IIIA(N2) og IIIB ca 20%, 5-årsoverlevelse ca 15-20% Avancerede IIIB og IV ca 50% median overlevelsen er mdr

12 NSCLC Behandling Lokal sygdom: OP og kemoterapi Lokalavanceret: kombination af kemo og stråleterapi Avanceret: kemoterapi/ biologisk behandling og palliativ strålebehandling

13 Lokal avanceret sygdom IIIaN2 og IIIB Kurativt intenderet radiokemoterapi 3 serier carboplatin/vinorelbine med konkomittant strålebehandling 60Gy/30F ved 2. serie Kontrol hver 3 md. på onk afd.

14 Behandlingsudvikling indenfor NSCLC avanceret sygdomsstadie BSC Cullen Monoterapi platin Sandler Older doublets (EP) Bonomi mdr. 7.6 måneder 7.6 måneder BSC = Best Supportive Care MI(V)C = mitomycin, ifosfamide, (vinblastin) cisplatin EP = etoposide/cisplatin Triplets (MIC, MVP) Danson Third generation doublets paclitaxel/cisplatin) Rosell måneder 9.8 måneder Docetaxel/cisplatin) Fossella E måneder 12.3 måneder Median overall survival (måneder) 1. Cullen et al. J Clin Oncol 1999; ; 2. Sandler et al. J Clin Oncol 2000; ; 3. Bonomi et al. J Clin Oncol 2000; ; 4. Danson et al Cancer ;2003; 5. Rosell et al Ann Oncol 13: ,2002; 6. Fossella et al J Clin Oncol 2003; ; 7. Sandler A, et al. N Engl J Med 2006

15 NSCLC histologi Non-squamous (2/3 patients) Squamous (1/3 patients) Adenocarcinoma* Large-cell carcinoma Tailored therapy Squamous-cell carcinoma Behandlingen individualiseres udfra karakteristika som histologi og biomarkører *Includes bronchioloalveolar carcinoma

16 Considerations for optimising treatment outcomes Biological characteristics Histology Molecular markers Clinical characteristics Performance status Comorbidities Age Tumour location History of haemoptysis Optimal outcomes PFS OS RR Disease control Symptom control Treatment tolerability QoL

17 Hvad er målrettet behandling?

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20 Ikke-småcellet lungekræft - adenocarcinom KRAS EGFR ALK MET PDGFR ROS ERBB2 BRAF PIK3CA MEK1

21 IPASS: Phase III study of IRESSA versus doublet chemotherapy in first line NSCLC Patients Adenocarcinoma histology Never smokers or light ex-smokers* PS 0-2 Provision of tumour sample for biomarker analysis strongly encouraged Asians IRESSA 250 mg/day n=609 1:1 randomization Carboplatin AUC 5 or 6 and Paclitaxel 200mg/m 2 3 wkly n=608 Endpoints Primary Progression free survival (non-inferiority) Secondary Objective response rate Quality of life Disease related symptoms Overall survival Safety and tolerability Exploratory Biomarkers EGFR mutation EGFR gene copy number EGFR protein expression * Never smokers: <100 cigarettes in lifetime; light ex-smokers: stopped 15 years ago and smoked 10 pack yrs Carboplatin/paclitaxel was offered to gefitinib patients upon progression PS, performance status; EGFR, epidermal growth factor receptor Reference: Mok et al NEJM aug

22 IPASS: EGFR mutation is a strong predictor for differential PFS benefit between IRESSA and doublet chemotherapy Probability of PFS Treatment by subgroup interaction test, p< IRESSA EGFR M+ (n=132) IRESSA EGFR M- (n=91) Carboplatin / paclitaxel EGFR M+ (n=129) Carboplatin / paclitaxel EGFR M- (n=85) EGFR M+ HR=0.48, 95% CI 0.36, 0.64 p< EGFR M- HR=2.85, 95% CI 2.05, 3.98 p< Reference: Mok et al NEJM aug Time from randomisation (months) 22

23 Clinical factors that independently predict EGFR mutation status in Caucasian patients ANALYSIS IN CAUCASIAN PATIENTS (INTEREST, INVITE, ISEL, INTACTs and IDEALs combined [n=786]) Smoking status p< Odds of mutation 6.5 times higher in never-smokers than eversmokers Histology p< Odds of mutation 4.4 times higher in adeno than non-adeno Gender p= Odds of mutation 1.7 times higher in females than males Other factors tested: Age (<65yrs, 65yrs), WHO PS (0-1, 2) Overall EGFR mutation positive rate 9.5% 23

24 Tal fra Aalborg pr

25 EML4-ALK fusion og crizotinib ALK: anaplastic lymphoma kinase i 2-7% af NSCLC kontinuerligt, abnormt aktiveret pga kromosomal rearrangement, som fører til expression af en oncogen fusion kinase, kaldes EML4-ALK EML4-ALK er associeret med ung alder, ingen eller ubetydlig rygning, histologisk adenokarcinoma kræftcelle, som producerer EML4-ALK onkoprotein er følsomme overfor ALK-inhibitor (Alice T Shaw et al. Lancet Oncol 2011,12: )

26 EML4-ALK fusion og crizotinib patienter (n=82) male sex- 43 age: 51 (mean), (range) ECOG: 0:29%, 1: 54%, 2: 16%, 3: 1% no. of previous therapies: 0:6%, 1: 33%, 2:18%, min.3: 41% histology- adenokarcinoma: 96% squamous-cell carcinoma: 1% other: 2% smoking history- never: 76% >10 pack-yr: 6%

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28 Acceleration i udvikling af ny medicin Chin L et al. Nature Med 2011,17:

29 Hvad er på vej? Immunterapi til lungekræft( planocullulær) 2.generations TKI Optimering af strålebehandling.

30 Molekylære targeterede stoffer under undersøgelse til lungekræft EGFR/HER inhibitors Lapatinib Matuzumab Panitumumab Cetuximab Tarceva HKI-272 Gefitinib Imatinib Phase I Angiogenesis AZD2171 inhibitors Phase II Vatalanib Sunitinib Phase III VEGF TRAP Approved Avastin Vandetanib Sorafenib Motesanib Other moleculartargeted therapies PF Talabostat Celecoxib Tipifarnib Bortezomib AS1404 CP Bexarotene AZD6244 RAD001 ABT-751

31 Cancer Treatment in the Future? "Here's my sequence The New Yorker