LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
7 r/ X' B! _( FTHERAPE UTIC PERSPECTIVES$ D8 r4 z, r" K! m
J. Mazieres, S. Peters
V8 C2 i' M0 K4 tIntroduction: 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
l! B4 f6 h2 i5 S4 c' h, Ooutcomes 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
& H! ]$ t& K9 R* K& Vtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
! Y1 Q. v, B5 ~9 h" f% vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations, I7 i+ \0 t* v, }( C. E; d
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;2 m$ `6 s. k; E) H- M+ q
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for! ]- v) O9 M( j
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to* l& E9 a6 d; P4 \/ y
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
: P# X1 K1 n" }. F2 a/ a( u22.9 months for respectively early stage and stag e IV patients.
* Y+ c! z+ y5 W( O* u8 CConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
I! A3 `5 i1 m" h( o9 treinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .# `' s: V w) r3 H
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
0 w" i+ \; m5 S' l8 W( L' x+ Vclinicaltrials.
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