LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% N% y! j* G3 [1 Q" {3 e# N/ N7 j
THERAPE UTIC PERSPECTIVES
% b5 x/ Y3 `& a, vJ. Mazieres, S. Peters/ i' f/ J! B" H
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
, U6 U* m/ ~7 w$ Uoutcomes 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
( m& p1 t, ]! c' I. }# ]treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2( m4 t. n/ C9 p, O s
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
; G* p: D1 @% ^! \ z, r0 {and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
0 d; y% m5 o1 w% z& n! v- s. gdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for& @! q, l7 G1 P- S! j! \
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
* O! z- ^% `; g7 Blapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
9 z8 G. ~% t# l8 [- U* \! Y22.9 months for respectively early stage and stag e IV patients.
9 S0 j ]" ?- \1 y: q: bConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,5 q, B( v& k% e% D% d# G6 R% Y
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. e @- y8 K& PHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative# k; X# n+ m0 ~. a1 H
clinicaltrials.
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