LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
" W( w) t: U+ `3 B' ]6 y7 XTHERAPE UTIC PERSPECTIVES* f3 H; B- Z4 q% h" X8 g. \
J. Mazieres, S. Peters
+ L4 O* C7 P$ l; bIntroduction: 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
1 M1 C7 y, L a- @3 _. i+ F) ioutcomes 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
" n' I( }8 G4 Z2 n) o2 I' \- I: wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
: }; P7 q+ X+ W2 {/ C3 v Qtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations+ l: Y( z5 e/ }( d# [
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
; | \5 F0 K1 P. H* U& K% E8 ndisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
9 _7 [; {. _% u. A% {+ d- [8 w2 Ctrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to3 r% U, X" K$ o
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
: B( ^1 _8 `7 g1 e22.9 months for respectively early stage and stag e IV patients.
4 N" l. l7 }& L5 N j2 w8 y) ~Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,6 H" d6 t5 d$ X( {0 V/ \8 _% B8 l
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
1 C! x: Q7 ^- B3 N1 fHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 x" k9 n9 w- ]4 s. H
clinicaltrials.. t' P9 q; Z% ?) C
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