LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND2 g7 p( b9 W7 J8 E8 x& ~
THERAPE UTIC PERSPECTIVES$ O0 P" H9 K2 F& J7 j
J. Mazieres, S. Peters
4 W; ] I+ |4 ~. ]Introduction: 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$ J" F2 S3 g1 }+ m2 w2 q3 {
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 targeted4 ?9 i: c$ E: S$ N, W( w
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
; ?, \. M! e+ }0 [' Ttreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
( `; x s# C, ~: b8 C% V! H3 I4 Nand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
5 k; ~: D0 O, a& } {: Y4 E: @$ wdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for& Z5 D" k% t7 O& K
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
& U8 @+ ?, F6 e: x# }& q% ]lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
9 S$ _; ^: J) K# L+ k22.9 months for respectively early stage and stag e IV patients.
% {, R* w+ o$ u0 L% i/ IConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
5 I' j( g: x% O" yreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
; u7 c' ^4 ]' O" ^$ P5 |! x! PHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 j7 a5 Q% V8 ~; u4 \. k* pclinicaltrials.
k. _& C, R5 p$ y! ] |