LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND8 M8 s9 h* E4 z/ a
THERAPE UTIC PERSPECTIVES; s6 t1 Q$ m7 [. K% _$ p# v' H3 }
J. Mazieres, S. Peters
" @$ j9 e$ o- {; R# hIntroduction: 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
/ N' s& L& P) R# Toutcomes 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
2 t" }- l/ ]. q# f: ?7 P( {treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her26 r+ e- o( V( C! c2 o4 A* n
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
: E! V9 `0 k t6 ?8 Z# Aand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;' t1 o4 Y- ^0 s! ~" Y, o# l% V2 t8 \
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for4 d* v9 @! m+ a5 }3 E/ |/ R( W
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
% G; y4 q- F0 H: Slapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and* Y& j: N) o" a$ }6 B; x6 D# f" G
22.9 months for respectively early stage and stag e IV patients.2 i: t) c& B' Y4 N' U; _
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,9 H. @* y: l: j+ I, O( b
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ., f, u# q7 Z/ b/ w: m, V4 k9 C
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative" Z3 [$ \1 C: p$ u
clinicaltrials.
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