LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND5 m5 {4 p9 H$ _
THERAPE UTIC PERSPECTIVES
& {% a7 U9 U9 [J. Mazieres, S. Peters: F& G0 M" `+ z* A& I) K( ^' u
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 therapeutic1 x( K- ]% l( X1 i) C4 T
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
$ T1 R2 l( M+ j2 o* Z& \9 ztreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
" ~' n* H3 \! [" P- C( T- ^: h# Wtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
+ z& N% g" h+ \: ^- sand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;9 x8 ~' s- s' w, O. F
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
# {+ S' L+ X3 R8 D- gtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to! X0 x4 V T7 I. m5 t6 z" r; V
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and# ]9 o l0 w$ [, ^5 y
22.9 months for respectively early stage and stag e IV patients.
2 S0 k3 b' z" M5 uConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
; r' @( f+ u' I3 _reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
! e' R4 {1 H" V0 X& gHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative7 {0 S7 z7 G' q4 s$ }3 n
clinicaltrials.+ p) l4 i! W: a# y( A9 c$ y
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