LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
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J. Mazieres, S. Peters
, P9 z; g5 H. ^+ A+ W( I) eIntroduction: 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 therapeutic5 r" r4 t5 t2 D& X! l
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
6 e( n4 z5 l* [/ h( J/ ftreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
/ i' }. s# ?1 q0 j& ztreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
& A& w6 l5 l+ a: ^ a4 [and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
0 o0 r1 N8 Z$ pdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for b6 G+ E7 {" E& ~& f! Q( W
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
B0 {6 J: B+ J9 N1 klapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
1 v% ^$ t2 R* @5 t* p( ^' ^8 s22.9 months for respectively early stage and stag e IV patients.
1 N5 v/ x- e2 o+ w* c# D* e( KConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,( j1 a) C4 u# c1 D2 t$ r9 ^4 P& _
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ., W7 o9 v; V0 Y) H( \% A9 k) r
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative8 Y) p& g8 w- H4 q- r% I6 O1 D/ a
clinicaltrials.
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