LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 f9 i1 g0 _/ ~& N
THERAPE UTIC PERSPECTIVES5 v& Y: ^( }- X A+ @+ Q5 y& J
J. Mazieres, S. Peters2 I$ B8 [$ N: l# y
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 therapeutic6 l) ]$ V" K: u
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
7 t, E: [% H: b! }1 ltreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
3 r* U, C# y+ J v0 utreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
! R8 a, E( M3 o" g Kand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
' m8 |5 R/ q' R: Fdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for0 s* W2 R: a( E( `/ R' b
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to. z( F" H2 \: p9 v: d) a
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and. w: p3 n" D5 h/ H# _6 q% i7 n6 f
22.9 months for respectively early stage and stag e IV patients.
1 C U+ \1 b! R/ H) AConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,; Z2 e3 d6 ]/ e
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. m, @: n: A& V cHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
- g" O2 l# N9 `8 v3 Zclinicaltrials.
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