LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND; i, z( b5 |% g" J4 I3 Z' D7 U( g
THERAPE UTIC PERSPECTIVES
& D" E1 [9 Z3 _/ ~J. Mazieres, S. Peters
4 F/ w) m5 w- H5 IIntroduction: 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+ m R m7 i6 ], Q
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
' i, I# b; b) V- X5 F- s$ \" ntreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
9 @1 [9 D* x# S! Qtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations+ P- J, Y% r6 \* l, {
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;4 {% N# X, \- m" _" E- c! U
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for' S0 p3 c* d1 E' T, j
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
' J* y9 o5 T! o2 `7 E! llapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
* [+ p9 F3 R& u% C9 k22.9 months for respectively early stage and stag e IV patients.
. G1 ^/ N0 C! [) l, a2 N# eConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC," B" ?' L$ L, {5 q& Z7 ~6 N. Q6 i- U$ X. H
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 ?4 L# b2 K$ z8 H$ p
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative& L4 w6 n+ [8 R0 v3 c0 h) o
clinicaltrials.
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