LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND& l2 Z9 X6 ~* J( t- H# R' e9 O% p. t* [
THERAPE UTIC PERSPECTIVES
5 ]' v- j6 z* [J. Mazieres, S. Peters
t8 y1 @" V2 J. ^ NIntroduction: 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' F7 ^! {4 K) h, a f) n; h
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
8 y0 D5 f. P& D+ l6 P% a; Ntreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her27 x" z% \" t, J
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations! w4 J! z) `5 x9 w. M
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: q4 [+ e; x# L: f& r b7 R: Gdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for. _) R7 z& X' I4 Q2 V/ F
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
! ^; L3 B1 k3 ^$ m+ \4 t& Slapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and# z2 X* N A! C: F" z# E
22.9 months for respectively early stage and stag e IV patients.
6 u! S' D. U. G* f5 y+ d5 EConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
' b+ W( J$ `+ d' o) G7 E+ qreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .+ [0 S0 Q6 Y' T0 U
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
" R1 p1 H& \$ _, e2 j- i1 Oclinicaltrials.( B8 P9 o2 d; y
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