LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
5 t+ ]4 e! `$ a! O, FTHERAPE UTIC PERSPECTIVES
4 ^: p+ c; ?) |" w4 yJ. Mazieres, S. Peters
" j, v7 }9 u0 l9 x$ |/ @( b& n6 R" HIntroduction: 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
% `! ]8 X1 t* b6 U' Coutcomes 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 targeted5 i) S. G' c. a& }" m4 I5 Y
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
5 a. ]# q+ }5 d2 k0 G3 f- x! qtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
, _6 m+ K& w) y% ?$ M6 pand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
3 J& F" G2 Q5 y6 E0 ^7 e. Ldisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for; z' g* y2 j, G( w
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to: B+ `; e' T/ X5 z- R& m
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
4 O: o" K* U* P5 L# {22.9 months for respectively early stage and stag e IV patients.
2 u, x6 \' h1 s2 n7 c7 c7 t; eConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: S8 K3 g# ]% i0 e1 P' I. s: I
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
: G6 ] b2 \& P- y3 B5 M5 y! y; SHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
) |* h5 @5 v" D* Iclinicaltrials.# K, J' y7 _' p w& K: f) m
|