LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
; d) s1 ~: [) V! o0 RTHERAPE UTIC PERSPECTIVES
' l! F; |, H) z( }9 i: ^J. Mazieres, S. Peters
% ]* d) F( V F y. \, 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
, S4 R& T; c% X' z0 }+ U8 ~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$ o- A: T% m- c) e$ Y
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
) N1 F# I+ [, [0 }0 R% K7 @treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
% S9 S5 U, ]! G+ U i3 S% ?and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;7 j1 {& e" V) E$ H; T: e Y+ q1 S
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
. V {3 i4 o8 }6 ~4 ktrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to6 k9 I+ y& h# \
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
/ I. |' n5 _# o( k22.9 months for respectively early stage and stag e IV patients.
$ g/ Y" |& S2 ?7 B5 [5 lConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,) J3 y7 d) D4 N4 ^0 P
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .* ~- @. s5 r$ _ ^$ S) q; W
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative# ` i* Z3 U- ~. N" J& B
clinicaltrials.
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