LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND# M+ t, a, f' Y) [$ I- x' T
THERAPE UTIC PERSPECTIVES2 K" U! |: g/ S: E: D; f
J. Mazieres, S. Peters
' i6 n. l& k5 ^) R# ?5 a' G" mIntroduction: 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; P( r9 w( W6 v. }4 v( o& A+ u3 k
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- _" h. ?5 L! ]
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2) \# e; z3 p2 K' n* F: f
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
: t; o( g, N4 `+ m) y& gand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;+ z, ^2 b' N- F. V. t
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
$ G2 D [/ @$ U/ R, F; K3 strastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
& a6 [- ~* _8 Ulapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
- c. t( u" b6 T$ M9 x! |% I. ?22.9 months for respectively early stage and stag e IV patients.( _. ?9 Z$ L6 ^6 Y
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,4 |2 r7 C) h8 `& a
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ., Y# o, l' ?/ ^/ H5 ]/ F9 Y
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative9 | E j0 ]6 X% A# t2 z; |
clinicaltrials." Z9 ]$ @5 l; Q5 o3 X
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