LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
' x* {; j& q# sTHERAPE UTIC PERSPECTIVES- h: z. [$ b- g% }3 t) _) `
J. Mazieres, S. Peters
+ n* c& F) B& @, O3 U' k+ uIntroduction: 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. x0 s; J; d0 x! s3 b' T+ B7 ^ [
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 z7 g/ P. V" ^9 y4 n! w, C' O- H' j C; [
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2! Q; K8 {' x# l6 a! x
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations4 M9 X+ f+ b1 t f! Y0 j
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
9 T# r6 O$ j" o, b0 n: \disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
+ i: c4 B( w. O# t$ Z1 [- X$ _6 Q* Ntrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
$ g0 ?/ g3 k1 f Ilapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and" r! Y) g' _ i
22.9 months for respectively early stage and stag e IV patients.1 Y5 z" e: u/ r
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
% t V( |1 i: k4 L e5 z% t& Hreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ., r# J7 Y* J% r) ~' Y4 F, V) N
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative4 i0 F- {! D0 g
clinicaltrials.
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