LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
0 t2 d- [3 C' S7 gTHERAPE UTIC PERSPECTIVES" i1 H" y( z. o1 N! u- B
J. Mazieres, S. Peters, h3 D r9 ^0 b5 h5 D
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; f5 H' Y. O9 g, g
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
# C7 R+ w. I0 j9 q/ z5 O$ m. Ztreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her22 q: M, Z/ j( T. b* J% X
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 p: E/ }) p1 X2 G \: ^3 K! z
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
6 o0 Y3 l1 l& | G* G2 M) w. x3 xdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
$ M- a( G- m {trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to/ T6 G% v9 V; l5 }( Z
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and( b4 K5 ?; j8 ~
22.9 months for respectively early stage and stag e IV patients.( v% D& f6 B/ C" |6 v0 i2 G
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
6 I ? r. n9 H% q; mreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
3 k$ ~5 X9 ?2 N J. N/ EHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative2 J/ H' |/ X x3 K, ^; d- V
clinicaltrials., p, X s9 J# A6 K8 t& ^
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