LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND! I! f* `3 Y' m) n3 V8 ~
THERAPE UTIC PERSPECTIVES
7 J! N. B( L9 KJ. Mazieres, S. Peters, V j2 ^) s+ h9 ]+ k0 _6 I+ I
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) B+ c+ s. ]8 m( v3 T1 n, 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 targeted7 u# Z* b9 ]% Q6 |1 c
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2* _5 O6 L3 B/ Z/ q+ t$ \4 B
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations0 G* S G3 o; q+ h, P+ C
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
! d/ x, w [- a3 D; Tdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
, r; p( ^% B: b' t1 X: `trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to1 `& ]: }) _% i! K, S X
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
1 a! W( F D+ B$ K3 `% N( A22.9 months for respectively early stage and stag e IV patients.# k4 N5 {" O) p9 L" T
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
, _1 s" u5 `# O( y2 N/ p; J& lreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
* k5 e* s& c1 a, Y0 BHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative2 f9 g: k' P2 b$ L( o s* J9 P
clinicaltrials." `/ h5 W8 c) o
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