LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 s4 F4 D1 y2 m; D* a# _2 J
THERAPE UTIC PERSPECTIVES, z6 p. n8 w% m) F; i
J. Mazieres, S. Peters
% C9 _0 A0 v- D0 WIntroduction: 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" O4 p9 j- s) C$ A4 P7 |& l- x- Q q
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
1 S1 Z z4 p8 x" }9 c8 Ftreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
) N, B D- \3 {treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
; n5 g2 p6 p" O" Aand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
) H7 D d- W9 Y5 \+ d! Tdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for: C+ O" Q( [- ^: {% e
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to2 x1 a- i6 A( |6 H E: g# I3 p9 I
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
# m! ]+ ]" ?5 k. O/ E22.9 months for respectively early stage and stag e IV patients.
! H5 z0 t3 {) u- aConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
8 B0 X4 B3 c" V( f5 ]/ Yreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
* y5 U/ z( a5 _. T3 h" y! SHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative, C. L# h7 Y- u0 @
clinicaltrials.
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