LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
3 Y( r, H, q0 wTHERAPE UTIC PERSPECTIVES5 q0 n+ N- a7 {( t; X- R
J. Mazieres, S. Peters
# A8 ~8 E' f6 P6 m$ sIntroduction: 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$ X& [# w5 S, D8 K/ c7 |
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 targeted6 Q4 b# Y0 x, A! r5 {
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
! a7 ?2 K" P. a0 Z" M& Vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations! @) k1 C4 V! Q( d3 G# I8 Z3 s
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
& ^5 V( m/ [( Idisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for% _* [5 w2 \$ o4 p* b
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
% h f% J8 n9 x9 h. O* a* f! olapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
. P$ i7 N9 k) R9 F1 D22.9 months for respectively early stage and stag e IV patients.8 R- B# J. @* M+ u5 H
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,3 o, a+ E. i/ _+ C# J( J* j
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
" u4 z1 z6 ]# O1 nHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 f* s" C: b( |5 V+ w) k+ N+ jclinicaltrials., ^! [1 a _, V# T* J; r
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