LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
* Q3 i. O" ` mTHERAPE UTIC PERSPECTIVES
) q" N( f2 p& c7 x; f5 Q, ZJ. Mazieres, S. Peters
* g; Q1 i3 Z0 {8 N: n v/ yIntroduction: 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
6 H |+ M% o0 J0 Moutcomes 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 ^$ @2 [7 Z5 C3 a; jtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2% D% `& b, O7 E8 q
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
% U; n o$ _( n% Iand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
, h# I5 t! ^- z1 d( D- N3 _; ~disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
6 t! S( _/ U1 K) y% X- itrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
1 J4 ~* k7 Q* ^( M, Y/ e0 g6 Llapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and1 R9 ^: ?# k7 ^" P7 D( f
22.9 months for respectively early stage and stag e IV patients.6 w) z5 K: T0 t0 E
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,( ~7 z( P5 B6 R, M; z
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas . a9 E9 d* M6 F$ r# z
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative# Y5 \/ {7 L( `8 ~
clinicaltrials.3 h) U( m+ }" N9 n, ~- r- c- t
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