LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
7 d7 {" u7 c* ~THERAPE UTIC PERSPECTIVES
6 ?6 L: Y# p. E6 M. EJ. Mazieres, S. Peters
" B- W% j4 z0 ?5 |3 GIntroduction: 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
. D# a6 D: D& U. y, t5 D, F7 C# Foutcomes 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/ X/ M# I& `& j. ]
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her22 k' U0 m: l3 \, h9 K
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations3 R5 k" X; ?" X( ?5 [
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
9 Q* _1 ~: t- r0 J! T" wdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for1 `9 N$ x4 C+ M; z5 c! _, }
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to8 N4 h9 ^* Z8 [/ q S
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
& F0 L# E/ x1 }) l0 N22.9 months for respectively early stage and stag e IV patients.
3 J6 H+ I$ ]% z1 yConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,% q9 e8 ?* W4 `+ @
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
: q9 s+ T" m- n4 ]' d8 f, qHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
% h0 l5 O; P' j4 c$ N. Q! Wclinicaltrials.
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