LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
) a, W' {: ~( A: \ yTHERAPE UTIC PERSPECTIVES4 {7 i9 Q) U2 i) d7 n. R0 s/ t
J. Mazieres, S. Peters
$ s- Y' Q% D- H0 p! aIntroduction: 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
. w& c' p, w# f2 Z9 koutcomes 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
- g' e' l) L. Y& f( m) ^treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
9 c @" |. o4 f( Z- c2 Otreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations( L5 o5 Z2 L6 G7 s- \
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;2 ?+ m% m1 _3 c+ `9 \2 s& z# r2 f/ h
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for3 c1 d( H7 y! x# c( X
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to- O0 y( b I1 g, t9 B j3 ^( q
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and( u W2 r* p) m5 j* a6 a0 i
22.9 months for respectively early stage and stag e IV patients.
. ]1 T/ s( q+ Q) Z+ u r0 MConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
% E Y# c* _; |! Hreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. a a; e7 Q L7 ^HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative% Z7 r: H/ |) N6 M
clinicaltrials.
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