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NSCLC-metastatski (Target (Druge mete (STUDIJE (Umbrela, Basket), METex 14…
NSCLC-metastatski
Target
EGFR
EGFR
MAB
cet
cetux
cet+taxan ili combo, bez obzira na histo ili EGFR- nss OS (10vs11mj) i PFS (5vs5)
CV plus cet EGFR poz- FLEX-ss OS za 1 mj-11 vs 10 mj
TKI
1L
1generacija
gefi
registracijske studije SIW NEJm
nazivi
4 more items...
1L kombo
KT
1 more item...
erlo
registracijske studije
EU
1 more item...
OPTIMAL
1 more item...
enSURE
1 more item...
1 L kombo
VEGF
2 more items...
2 generacija
afa
LUXlung 3, 6
za EGFR rijetke mutacije
DacoTinib
ARCHER 1050
3 generacija
osi
studija
AURA3
1 more item...
FLAURA
1L kombo
1 more item...
rijetke EGFR mutacije
studije u tijeku
rezistencija
studije
2 more items...
leptomeningealna
BLOOM
nazartinib
sumirani dijagrami
studije
https://www.google.ba/search?biw=1229&bih=548&tbm=isch&sa=1&ei=EUznWp2ALKGC6ASsuoO4Ag&q=egfr+nsclc+first+line+study&oq=egfr+nsclc+first+line+study&gs_l=psy-ab.3...4023.6001.0.6281.6.6.0.0.0.0.309.918.2j3j0j1.6.0....0...1c.1.64.psy-ab..0.0.0....0.onyRwvpLS_w#imgrc=A4-LSxW-y11XJM
:
novi klinci
poziotinib
EXON 20
TAX 778
EXON 20
održavanje
EGFR w/m
Erlotinib, ssPFS 1 tjedan, OS, kod mut neg OS
ALK
ALK klinika
crizo 60% RR
studije
PROFILE 1014
2L
PROFILE 1007
ceritinib
1L
ASCSND 4
2L
ASCEND 5
alektinib
studije
1L
J-ALEX
studija
https://www.nejm.org/doi/full/10.1056/NEJMoa1704795
ALESIA +
https://www.youtube.com/watch?v=pNP545Idcf0
2L
ALUR
brigatinib
studije
ALTA
longest response
japan
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667864/
harvard
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659921/
PFS >5y
CNS
CNS
Njemačka studija
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205553/
review studija
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063430/
osnove
receptor
varijante
https://www.google.com/search?q=alk+receptor+variant&sxsrf=ALeKk03iGovM6Ube8mP5TEsj8pGUNrf6Kw:1596753021608&source=lnms&tbm=isch&sa=X&ved=2ahUKEwjdi5bF0IfrAhXIsaQKHSCwCm4Q_AUoAXoECAwQAw&biw=1600&bih=708#imgrc=0uEXMXTRIqWSpM
varijanata 2 najduži PFS
p glikoprotein
CC (crizo, ceri)
rad sa p (GP)
https://pdfs.semanticscholar.org/cc3b/6d62ba37cc23f96604a3b80dabed9e466130.pdf
manja koncentracija p gp
https://ascopubs.org/doi/10.1200/JCO.2006.10.0677
pet konentracija
VEGR
ramu
studije ramu+doc, REVEL, +OS, HR 0.88skvama
doce+ramu, adeno, REVEL, HR 0.83OS
dizajn
https://www.google.ba/search?q=revel+study&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiAz8CPz-LaAhWr0aYKHdX5DSQQ_AUICigB&biw=1229&bih=548#imgrc=SXMzVWC7nKuHNM
:
rezultati
https://www.google.ba/search?q=revel+study&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiAz8CPz-LaAhWr0aYKHdX5DSQQ_AUICigB&biw=1229&bih=548#imgrc=I8k3B7PbpwEBFM
:
ninten
doce+ninten, 2L, adeno, LUME lung 1 trial, HR 0.83 OS
dizajm
https://www.google.ba/search?q=lume+study&source=lnms&tbm=isch&sa=X&ved=0ahUKEwi9hLPTzeLaAhVEEpoKHcxXBxUQ_AUICigB&biw=1229&bih=548#imgrc=lSTp_0jQR-Fy6M
:
adeno
https://www.google.ba/search?q=lume+lung+1&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiZ97ONzuLaAhVrMZoKHTfNBckQ_AUICigB&biw=1229&bih=548#imgrc=Mv9UWecmaCLooM
:
adeno, plano
https://www.google.ba/search?q=lume+lung+1&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiZ97ONzuLaAhVrMZoKHTfNBckQ_AUICigB&biw=1229&bih=548#imgrc=iYFAVe-ByhHtRM
:
doce+ninten, 2L, adeno, LUME lung 1 trial, HR 0.83 OS
bev
ciljana th
beva
TC +/- bev- ECOG-OS ss 12.3vs 10.3, PFS ss
ECOG 4599
dizajn
https://www.google.ba/search?q=ecog+4599&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiNtLe_y-LaAhVDb5oKHTReDmYQ_AUICigB&biw=1229&bih=548#imgrc=3T9EnSixBIa0lM
:
rezultati
https://www.google.ba/search?q=ecog+4599&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiNtLe_y-LaAhVDb5oKHTReDmYQ_AUICigB&biw=1229&bih=548#imgrc=IbnBPRnzV3evAM
:
CG +/- bev -AVAIL- neg OS 13 vs 13, ssPFS(6.1 vs 6.7)
AVAIL
dizajn
https://www.google.ba/search?q=avail+study&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjotOLmy-LaAhUPyqYKHS6uC08Q_AUICigB&biw=1229&bih=548#imgrc=nnfKauudkSkvqM
:
nec
nec
CG plus nec, non i sq-OS 11.5vs10 mj ss OS
SQUIRE
dizajn
https://www.google.ba/search?biw=1229&bih=548&tbm=isch&sa=1&ei=1VnnWu6HG6XM6ASTnpmQAg&q=SQUIRE+study+nsclc&oq=SQUIRE+study+nsclc&gs_l=psy-ab.3...2151.4930.0.5228.8.7.1.0.0.0.166.716.0j5.5.0....0...1c.1.64.psy-ab..2.0.0....0.xiO2lrwIDuc#imgrc=VA7-xb5wvoerPM
:
rezultati
https://www.google.ba/search?biw=1229&bih=548&tbm=isch&sa=1&ei=1VnnWu6HG6XM6ASTnpmQAg&q=SQUIRE+study+nsclc&oq=SQUIRE+study+nsclc&gs_l=psy-ab.3...2151.4930.0.5228.8.7.1.0.0.0.166.716.0j5.5.0....0...1c.1.64.psy-ab..2.0.0....0.xiO2lrwIDuc#imgrc=ElpJNPinxzRl_M
:
Cpeme, non sq plus nec-nss OS
INSPIRE
dizajn
https://www.google.ba/search?q=inspire+study+nsclc&source=lnms&tbm=isch&sa=X&ved=0ahUKEwj4lpODy-LaAhUEEJoKHWesAcYQ_AUICigB&biw=1229&bih=548#imgrc=dticcsaZmP61zM
:
ROS
crizo 40% RR
rezistencija na ciljanu th
Th rezistencija
2 tipa
primarna
tumor intrinzični ffaktori
https://www.youtube.com/watch?v=zpHcLxD8Drk
3 podtipa
koegzistirajuće genetske alteracije
https://www.youtube.com/watch?v=C8OL1MTbGpU
koeg mutacije u signalim genima
https://www.youtube.com/watch?v=mvM2eyk1frk
inaktivacija proapoptičkih putova
https://www.youtube.com/watch?v=lYLn4CLCD8A
pacijent specifični faktori
https://www.youtube.com/watch?v=XUeAg25azU8
2 podtipa
plazma drug level
https://www.youtube.com/watch?v=eXRJfU2nzv4
drug-drug interakacija
https://www.youtube.com/watch?v=XDisE_VlR6c
stečena
4 tipa
target modifikacija
https://www.youtube.com/watch?v=0HX039UdGpU
bajpas
https://www.youtube.com/watch?v=3Nf6Q2skGOM
histološka transfomracija
https://www.youtube.com/watch?v=LNNMYwF7dHg
drugi mehanizmi
podtip
povećanje produkvcije faktora rasta
1 more item...
Druge mete
METex 14
GEOMETRY 1
Capmatnib
ROS
BRAF
RET
BLU treba ime
pralsetinib
AROW
https://www.onclive.com/view/liu-lends-insight-on-highlights-from-asco-2020-in-lung-cancer
NTRK
Entrectinib
HER
DESTINY-Lung01 trial
trastuzumab deruxtecan (DERUEKSAK :star:
:check:
https://www.onclive.com/view/trastuzumab-deruxtecan-shakes-up-her2-mutated-nsclc-treatment-paradigm
KRAS G12C
AMG 510
https://www.onclive.com/view/dr-pennell-on-challenges-with-ngs-in-lung-cancer
DDR2
dasatinib, Nilotinib
FGFR amplifikacija
FGFR TKI
PIK3
PIK inhibitori
STUDIJE
Umbrela
Basket
ALGORITMI
PRIME, CPI
http://www.primeoncology.org/online-education/solid-tumor/va-lung-cancer-series-2018-slides/activity/?login
ESMO
https://watermark.silverchair.com/mdw326.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbAwggGsBgkqhkiG9w0BBwagggGdMIIBmQIBADCCAZIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMewJo_3nBzaXBoQm1AgEQgIIBY9R_KvZqzg380aVbf59G7bDUni49j5LCz3XQD4DkNyOguyiT5gSyGbbUbW-uTDlFwZ1W9L7E0YAV1BBX1F_o5S0vSWspgokxMQFXmeljxuGhBFBuUmzrcp2rCYXL61iYQzvjAltTi0t6DYJk4OfcqcHt4uvqNr9YeSYLi8orfQzkBhw29FB-ljNiOdvQb9OeIiOkXAWeX2xwi_44BE-NLvwLu0ic9HWkLHsWP4QfPDcfDiAIH68rhpYjiy5jKPqOT6hdzeH8Ts0kYPJAnH9OqWAFWf3pRLgnGC05AwFpbRvYNdCFcYPxG2ymCacn91I3fVbXlyEvZk1IC75Ju01f7Mnwf7gGvZVgRMz7YcbYpHBc0DJjvcxlQXNVSV5vhpaUzD-DWU-XP1iNCSu93yuFm9KvRTu85JrOiEz5yqfypyCZODi_ffW9drFQU8anqumCdqOGI_BZZqE0Aihp1vh55qSRlbM
timeline
EGFR, ALK
https://www.google.ba/search?q=nsclc+timeline&source=lnms&tbm=isch&sa=X&ved=0ahUKEwituuiU0OLaAhWIx6YKHfuzBf4Q_AUICigB&biw=1229&bih=548#imgrc=Fpn2_ASHhVlguM
:
EGFR
https://www.google.ba/search?q=nsclc+timeline&source=lnms&tbm=isch&sa=X&ved=0ahUKEwituuiU0OLaAhWIx6YKHfuzBf4Q_AUICigB&biw=1229&bih=548#imgrc=e8gsa8AhSTXftM
:
KT, target
https://www.google.ba/search?q=nsclc+timeline&source=lnms&tbm=isch&sa=X&ved=0ahUKEwituuiU0OLaAhWIx6YKHfuzBf4Q_AUICigB&biw=1229&bih=548#imgrc=qQNP5tr5meSk-M
:
NCCN
https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
presjek terapija
https://www.google.ba/search?q=nsclc+TNM+illustrated&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjnq-WLuOXeAhXpw4sKHXtYBdkQ_AUIDigB&biw=1920&bih=969#imgrc=2qHOFXizCphnnM
:
PLAN LIJEČENJA
Driver
https://www.google.com/search?q=non+small+cell+lung+cancer+therapy&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiT64Xx_KLgAhVMbFAKHfabDvwQ_AUIDigB&biw=1218&bih=582#imgrc=EbFzqiyFiu7FcM
:
LAD
https://www.google.com/search?q=non+small+cell+lung+cancer+therapy&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiT64Xx_KLgAhVMbFAKHfabDvwQ_AUIDigB&biw=1218&bih=582#imgrc=UqIWQodfZ2al2M
:
Svi
https://www.google.com/search?q=non+small+cell+lung+cancer+therapy&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiT64Xx_KLgAhVMbFAKHfabDvwQ_AUIDigB&biw=1218&bih=582#imgrc=0K4zqTOIttNnXM
:
Rani
https://www.google.com/search?q=non+small+cell+lung+cancer+early+stage+therapy&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiZmtWf_qLgAhVEtYsKHTv4D3QQ_AUIDigB&biw=1218&bih=582#imgrc=oKGYxNNqFfT_-M
:
RT
BRT endobronhalno za palijaciju
PCI uloga-4RCT ne
WBRT, SRS; NCCN MS 24
multiple
faza 3 nisu kandidati SRS ili OP
BSC (dexa) vs RT+Dexa=OS
IMRT sa izbjegavanjem hipokampusa
može SRS
u 2 slučaju
mal V bolesti na periferiji
dobar ECOG
WBRT
limitirane
SRS +WBRT
lošije kognitivno
OS isti
smanjen IC povrat
neurokognitivno <AE
studija 1-3 meta mozga
C34; < sa SRS vs WBRT
ALK
prvo ALK inhibitori
2 opcije
OP +
SRS ili WBRT
SRS
30-50% meta mozga
Kemoth
kemoterapija
Konsolidacijska
studije
KT
SWOG
konsolidacijska kemo nakon CRT- ne (Docetaxel)
Old vs new
combination chemotherapy
Cochrane Collaboration; dublet vs 1- RR veći, OS 1y s 30 na 35%, AE veći - 1.2 do 6; 2 vs 3 - OS nss
nekoliko meta analiza cis vs carbo-pokazali bolji ORR s cis, nss povećanje smrtnosti s carbom, AE veći s cisom (n/v, rt) a carbo veča trombocito
platinum vs neplatinum, meta analize bolji ORR, OS s platinom
CG vs TC- ECOG 1594-nssOS
dizajn
https://www.google.ba/search?q=ecog+1594&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjpptW0uuLaAhWlIJoKHf9NBmMQ_AUICigB&biw=1229&bih=548#imgrc=JtRv5SRPPjlSRM
:
rezultati
https://www.google.ba/search?q=ecog+1594&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjpptW0uuLaAhWlIJoKHf9NBmMQ_AUICigB&biw=1229&bih=548#imgrc=DNNLuPnv_TRCsM
:
održavanje
nesqvama
pemetrexed
PARAMOUNT
dizajn
https://www.google.ba/search?q=paramount+study&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjkzbTq6IraAhVLb1AKHYqXBusQ_AUICigB&biw=1229&bih=587#imgrc=aU8tNiIdqlrNPM
:
rez-PFS+1 mj, OS+ za 3 mj
https://www.youtube.com/watch?v=kLl4b_doNtk
peme/bev
POINTBREAK
https://www.ncbi.nlm.nih.gov/pubmed/24145346
AVAPERL
https://www.ncbi.nlm.nih.gov/pubmed/24585722
općenito
povećani
PFS
toxičnost
ne povećani
OS
QOL
PHD
mutacije
NGS
https://www.onclive.com/conference-coverage/asco-2018/ngs-established-as-most-cost-effective-genetic-test-for-metastatic-nsclc
nakon 4-6 ckl KT
skvamo, neskvamo
Lancet 2009
rez ss neskavmo, 2mj PFS, 2mjOS, odgoda boli, slabijeg apetita, manje 2L primili s peme
druga linija KT
Shepardica
Doc vs BSC, bolji Doc
de vita 839
BR21, Erlo vs BSC, bolji Erlo OS
https://www.nejm.org/doi/full/10.1056/NEJMoa050753
gemcitabne
doza
dose of 800 to 1,000 mg/m2 , intravenously, over 30 minutes. The dose is repeated every week for 3 consecutive weeks, followed by a 1-week break.
periferni edem
https://sci-hub.tw/10.1097/01.COC.0000017782.24458.DD
vinorelbine
st IV
drug and dose schedule
partner Doc vs vinorelbin, bolji ORR s doc, manje AE
1 ws 3 tj, nema razlike u efikasnosti, tolerabilnosti
CG vs Cpeme - JMDB studija- os 10.3 vs 10.3; adeno i LCC SS, poboljšanje CG plano
Factors influencing treatment
histologija
adeno
beva
egfr
pemtrex
godine vs komorbiditeti
benefit dublet
vino vs BSC >70y
Docetax vs vino, PFS SS, OS poboljšan
PS
Cpakli vs Pakli, CALG 9730, PS-loš MS 4mj; arm CP bolji ORR, OS
Cpeme vs pem, OS ss Cpeme- ECOG 2
PSoslabljenni CG vs TC, PS2, poboljšanje OS i ORR CG - ECOG 1599
KT, MS 28
PS 2
adeno
kemoth
platin/peme manje toksičan od taxana
rezultati POINTBREAK
random
https://www.google.ba/search?q=pointbreak+study&rlz=1C1VASI_enBA525BA526&source=lnms&tbm=isch&sa=X&ved=0ahUKEwicz4yKoobfAhWRKiwKHfa1CTYQ_AUIDigB&biw=1396&bih=686#imgrc=dzRj8JZGhJ4HHM
:
NE, necitumab
https://www.google.ba/search?q=necitumumab+nsclc&rlz=1C1VASI_enBA525BA526&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjA7qa9oYbfAhWLhqYKHX1cCG8Q_AUIDigB&biw=1396&bih=686#imgrc=CH2Aylo0YICzAM
:
Općenito
30-40% 1yOS
protokoli
skvamo, mekvamo
stadij IV
nepoznate mutacije
baza platina
Imunoth
Lekcije
sigurnost
famakokinetika
CNS
Biomarkeri
periferni
tumorski
toksičnost
znamo riješit
kortikosteroidi
metastaze
jetra
mozak
trajanje
LTS
kombo
PD(L)1
anti CTL4
RT
Rezistencija
sumarizirano
Imuno vs KT
1L
KN 24 (42) 26 IM 110-NOć Rana Nar snažna Mistika
NIvo
CM 026
Pembro
KN 024
KN 042
021
kohorta G
Avelumab
JAVELIN LUNG 100
2L
Atezo
OAK
POPLAR, f2
Pembro
KN 010
Nivo
CM 17
CM 057
KITvsKT
1L
IM 130, 131, 132, 150
KN 189, RuSaK (407)
Nivo
CM 227 na NoGama :red_flag:
POSEJDON
IT+ITvsKT
1L
CM 227, Mistični Neptun
Durva+Treme
MYSTIC :red_flag:
samo IT
mono IT
1L
Nivo
CM 012
Atezo
BIRCH
Pembro
KN 001
2L ili više
Durva
ATLANTIC
Atezo
BIRCH :red_flag:
2L
3L
Nivo
RWD
Hrvatska
Italija
Pembro
KN001 :red_flag:
duo IT
Durva
2L
Durva+Treme
Atezo+Tiragolumab :star: (Tigro)
https://www.onclive.com/view/novel-antitigit-agent-tiragolumab-plus-atezolizumab-impresses-in-nsclc
IT+IT+KTvsKT
1L
Nivo+Ipi+KT
CheckMate-9LA
https://www.onclive.com/view/liu-lends-insight-on-highlights-from-asco-2020-in-lung-cancer
rani BSC
ENEBLE 3, 68vs48%y OS - 11.6vs8.9mj, 207 pts (40% lung)
