LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND1 B+ u' r9 X+ ]3 c7 a/ ?
THERAPE UTIC PERSPECTIVES
/ _* j0 V* G" K. CJ. Mazieres, S. Peters0 N# C) m4 |8 g+ G. y" t
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 therapeutic
: M, A! \) o& U) {5 H, A# Youtcomes 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- Y! p+ t0 \( U' U/ k
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
5 l3 S' w, O: B& Jtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations% n l& v! X2 x4 Y4 {* E$ ~5 W+ }$ y$ I
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;. o9 Q" j2 F8 j/ E4 x) T
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
3 L9 n7 s& W- t1 f4 d: W9 Q4 rtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
( M9 n7 x1 u% z6 ~( X5 Q! x3 Flapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
/ K0 X, R% s, l! i$ m9 X22.9 months for respectively early stage and stag e IV patients.
, v) w$ X% i& K; Y" GConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
" A4 e. \8 d# C- H/ freinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
y# K* i& P( G3 t6 J1 vHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative3 y/ `6 _ M+ U7 k
clinicaltrials.# S% C7 U7 l; K* K* E+ a) y
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