Här kommer första rubrik

Rapport från ASCOOch kliniken
Målstyrd behandling vid lungcancer
Karl-Gustaf Kölbeck, öl, sektionschef
Lung Allergikliniken Karolinska Universitetssjukhuset
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, 2014
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Evolution of Identification of Genomic Alterations in Lung Adenocarcinoma
Presented By Pasi Janne at 2014 ASCO Annual Meeting
Management and Future Directions in NSCLC with Known Activating Mutations
Presented By Daniel Costa at 2014 ASCO Annual Meeting
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?
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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
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
Background: afatinib
Presented By James Yang at 2014 ASCO Annual Meeting
Afatinib: Överlevnadsdata från Lux Lung 3 och 6
Combined OS analysis: mutation categories
Presented By James Yang at 2014 ASCO Annual Meeting
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
Could Low Crossover <br />Explain the Difference?
Presented By Howard West at 2014 ASCO Annual Meeting
Relevant Comparison for Afatinib<br />in 2014 is to Other EGFR TKIs
Presented By Howard West at 2014 ASCO Annual Meeting
EGFR TKIs and EGFR mutated NSCLC:<br />major mechanisms of resistance to EGFR TKIs (2)
Presented By Daniel Costa at 2014 ASCO Annual Meeting
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 2014
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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
Tumor Shrinkage Seen in Intermediate <br />and High MET Cohorts
Presented By D. Camidge at 2014 ASCO Annual Meeting
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 2014
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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
Study design
Presented By Terufumi Kato at 2014 ASCO Annual Meeting
EGFR Regulates VEGF in <br />EGFR Mutant Cell Lines
Presented By Howard West at 2014 ASCO Annual Meeting
PFS by EGFR mutation type
Presented By Terufumi Kato at 2014 ASCO Annual Meeting
Cost Considerations with <br />Erlotinib/Bev Combination
Presented By Howard West at 2014 ASCO Annual Meeting
JO25587 PFS in Context of Other Trials<br />in EGFR Mutation-Positive NSCLC
Presented By Howard West at 2014 ASCO Annual Meeting
ALK-rearrangerad lungcancer:
 Företrädelsevis adenocarcinom
 Ofta yngre individer
 Aldrig rökare eller nästan
 4% av all lungcancer
Karl Kölbeck Lungcancerbehandling jan 2014
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Slide 20
Presented By Leena Gandhi at 2014 ASCO Annual Meeting
Slide 10
Presented By Leena Gandhi at 2014 ASCO Annual Meeting
<br />Crizotinib: selective inhibitor of <br />ALK, MET and ROS
Presented By D. Camidge at 2014 ASCO Annual Meeting
ASCEND 1: Ceritinib vid ALK+ NSCLC
Progression-Free Survival in Patients with ALK+ NSCLC
Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting
Overall Response Rate in ALK+ NSCLC Patients Treated with Ceritinib (750 mg daily)
Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting
Overall Intracranial Response Rate for Patients with Measurable Brain Metastases at Baseline
Presented By Dong-Wan Kim at 2014 ASCO Annual Meeting
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 2014
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Tack!
Karl Kölbeck Lungcancerbehandling jan 2014
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