LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
2 d$ g/ s: \/ M: F, r, E& Q: H C3 wTHERAPE UTIC PERSPECTIVES; B9 Z' { h& r0 x* c+ v
J. Mazieres, S. Peters
( c+ B8 E. g! v0 B% L: O DIntroduction: 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 therapeutic5 a7 w8 x6 S* {* P5 D8 t9 Y, j, ]
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
; ]; ]! f! Z8 Q* E7 j$ U* v% D& K3 Htreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2+ C' j$ F4 d; D
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
: X. x# w, ~/ z/ m- K, rand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
7 q0 a1 X" n( x, pdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for0 o' n; W) c. K- M4 Y
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
3 N; h# D" p7 x, }' plapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
8 c" l+ P# B- a; @* \+ g1 a22.9 months for respectively early stage and stag e IV patients.. J9 b8 v5 v0 B. ~& B! c
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
$ _0 F; ^/ h* S' yreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
9 ?9 y* e& U& P: C, j. h" RHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
7 j/ Z# [; c" X/ c! V; Pclinicaltrials.8 ^1 U) E. I/ m
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