LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND* k! H/ t+ C2 V; ?
THERAPE UTIC PERSPECTIVES' ?( N; h v+ P4 ^3 a# b
J. Mazieres, S. Peters8 i* n8 G" y2 K* i/ r% Z
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, f+ Q. I4 g3 C0 D
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
5 z. E5 I9 |$ B3 y/ Y' [5 qtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
# K' U% E9 g$ Ttreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations1 T8 @) }& |0 H8 D
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;$ ^1 V& _2 N9 |! F8 C$ z* ^
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
: t3 {% Z4 j! P9 ]trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
& ?9 `8 R# U# h( p* ~0 q: k, ~* plapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
2 t( i+ j* x! t1 V" Z0 N: R. F' n22.9 months for respectively early stage and stag e IV patients.
; E$ K0 {/ P9 V2 RConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
; R' L' o8 N) {! V% e) k# i- Oreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
, G( g1 x5 R5 \* _1 y8 YHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 i, d" i, m! ]
clinicaltrials.
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