LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND* ~$ a% R& I7 u6 [
THERAPE UTIC PERSPECTIVES1 d. i1 @# ` M Q. J! n8 {2 r
J. Mazieres, S. Peters. X$ A3 R7 b0 g: G5 u1 ?! E( a
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 therapeutic+ i0 S8 D5 u& \3 z* c+ U6 m1 _
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
, d2 f) P# }3 r1 o L5 z& S$ otreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her25 _5 q2 Z" O7 U# ] f5 v. Q
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations9 K- R* }: t- C& S
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;! g& t* }: G A2 W! r
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
5 R: L d& o. L& E; z5 \# ctrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to# } I8 X3 _6 [7 _2 w
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
$ C* U4 ]9 @# _9 T( e9 W22.9 months for respectively early stage and stag e IV patients.( \" E; N5 `1 E
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
8 }0 K( q8 o4 d5 U z" ^" ereinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
" j) o) R, n3 i* m1 F: nHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative& [; R% O, e- L2 h
clinicaltrials.
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