LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% ?; H/ ~- N) k. }% u r
THERAPE UTIC PERSPECTIVES
" l% l# F/ n* q s) Z0 i5 Y* HJ. Mazieres, S. Peters
! }. N4 M/ p) Q6 L c) 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# P7 J$ ?, ~! G8 f. |3 E. i( i L7 R; 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
f, p- e! a# _' vtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
2 I: P M3 u- q( Dtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations3 Q) J( Z- U- S, L4 X4 S3 t
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
7 n2 V2 h6 |/ h9 l) kdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 H# J# T, \" M' k# R$ q" u
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to3 P9 a% F; J% F9 G2 O5 e
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and6 g: c9 Z$ Q& d7 `2 ^* y
22.9 months for respectively early stage and stag e IV patients.
& H" \5 _/ }5 |, H' n5 v' EConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: r/ z* b( m1 m: X2 l
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
M5 c1 y0 B4 ^9 H! k4 QHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
% D' b' `/ ?/ {) q) _clinicaltrials.
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