LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND8 r, T# w" D/ y7 Q1 K2 P
THERAPE UTIC PERSPECTIVES
7 v! L% s F- m0 v JJ. Mazieres, S. Peters7 U8 J R0 l. C$ ?
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
" s* D" C) V$ Z( p& z% g) S& A- routcomes 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
* P6 a/ o0 O" m/ Rtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her27 i4 H# O& u% c4 U
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
+ \7 e% u9 n. O6 b; B$ Nand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
+ r/ u$ _: K; J9 Jdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for! F" V: l% d! ]) V. A
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to* P; T# @: Z' X% {0 t+ H
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and v" H0 r t1 W3 l
22.9 months for respectively early stage and stag e IV patients.
7 a! t- j# z% d2 G- ^. j* X" rConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,/ ]( M4 n, H; ]) H; T/ L
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
1 p l* Q- c; |) ^. J4 O+ b( fHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
7 q& _4 M. E2 a3 _6 T6 j7 x) Q' ~+ bclinicaltrials.
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