LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
9 \* Y+ t* C" s5 \& Z( ?THERAPE UTIC PERSPECTIVES$ }3 v8 `9 _% z/ H$ b
J. Mazieres, S. Peters+ X8 c" A4 J' F Z' N2 G
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 therapeutic3 P- L7 B8 Y5 ]* {" s( ?6 z
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
& B6 e9 _$ P& L# ~4 b3 p& L r1 vtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2: D6 m" \, c$ o1 v
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations6 {% J* L, w. g( Y& L" S
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
" U# b3 S- F! | V9 ]) Y, J* edisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
7 }8 l( m, _( B! ytrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to% F$ Z3 _. m/ z# V8 U7 N- p
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
8 V. {! _. n% J# s7 ~5 ^) T. T22.9 months for respectively early stage and stag e IV patients.
1 e9 @ G8 Y* B$ c. q4 O. |Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
4 q a" {8 f1 p. W6 u1 H% lreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .2 l$ ?' x1 u# j; m* v2 v
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative* I# f: p& A) z' `0 g5 E
clinicaltrials.* V4 p6 I) B* c. {, o
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