LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND$ ?; f3 w( o) w
THERAPE UTIC PERSPECTIVES
! r+ p- h* g/ P. jJ. Mazieres, S. Peters, ~3 L; S# O U x3 ]
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 therapeutic6 j! k0 s0 }* O
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
7 {% g1 W5 s2 e* ?: w. x8 u% p% Mtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her27 Q1 X) c' L! @ g0 l
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
. v o2 ?* F1 c9 D2 k& y( P# ]2 Hand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;/ k1 l& b' N3 P
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for4 F8 ~$ B: {, }( ~0 }0 s* }! D
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
; R' }! H9 |% z& r6 }- Elapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
0 L+ ]$ U& f8 ?/ ]% ?% c: k22.9 months for respectively early stage and stag e IV patients.* [1 J# V; j- I C- J
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
+ @' _0 A1 v8 U d5 {6 ^reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ., t: N/ M5 ~ b' L5 b+ W
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
% \5 h4 X) S$ j& V, J5 B! M: u Qclinicaltrials.
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