LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
: t2 Q f, {, b4 l7 nTHERAPE UTIC PERSPECTIVES9 f# ?" N2 Z i( g6 u. X5 N% C
J. Mazieres, S. Peters
; P1 l* z9 f" c1 M6 yIntroduction: HER2 oncogene is a memb er of the EGFR family, encoding atransmembrane receptor that drives and regulates cell proliferation. HER2 mutations are identified in about 2% of non small cell lung cancer (NSCLC) , mainly located in exon 20, and appear to be critical for lung cancer carcinogenesis . Very scarce data are available to define a clinical profile of the patients harboring HER2 mutated NSCLC. We aimed to study clinic opatholog ical characteristics an d therapeutic/ u$ P$ q$ \) a- r' s& d% f1 p V {
outcomes of patients harboring HER2 mutation in a large European series. Result s:We retrospec tively ide ntified 46 NSCLC patients diagn osed with HER2 exon 20 mut ation. HER2 mutation was mainly exclusive as only one concomitan t KRas mutation was des cribed. Our population was characterized by a median age of 60 yr (31 to 86 yr), a high proportion of women (30 vs. 16 men, 65% ), and of never smokers (24, 52%). All tumors were adenoc arcinomas (two with lepidic features). Half of the patients had stage IV dise ase at the time of diagnosis. HER2 targeted! |) Y$ [. F I9 O
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2% k5 W) r1 e" t* {
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations: K# }1 c$ A! w3 V- e4 v1 {8 v
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
; f( Z. k+ ^, tdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for+ I& ~- [. v5 M% Z' j# k, ]
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
6 W! X0 w# y$ R; x# x7 xlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
! W7 g9 w6 E7 M& Q+ X; P2 p22.9 months for respectively early stage and stag e IV patients.
. O# Q& ]) g4 ZConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,, |, n& X9 V7 B* r! @- e9 l
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .. e) W6 `" T2 @ g, S6 B
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative5 w0 ]+ R! ]% i; Z6 B: k0 \) a8 X" ~
clinicaltrials.$ G& _5 h, R8 M. A8 k6 K
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