LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
$ y6 H% ?4 h+ N0 eTHERAPE UTIC PERSPECTIVES
# u& D# g( w6 Y1 U% J4 v& OJ. Mazieres, S. Peters& @: k* h3 x% E! B" p1 ^6 f
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, u a$ h+ C* ?# b" I" q9 E6 n
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
- e( o" l1 P( H, I% c* j4 ftreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
6 y9 B1 M. _& Z* c& T4 jtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
6 F2 X) P* b8 L* n5 qand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
8 K, {; c5 P/ U8 u+ xdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
) t2 P% d. X) O8 o2 P3 L' ctrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to U7 o; @+ x) f4 C. G, t' j
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and; b& x' c( E9 W6 a/ t2 _4 d3 d
22.9 months for respectively early stage and stag e IV patients.
! K' w( S J# |) kConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,; Y0 d! M/ E5 ~% R# i0 U! \
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
+ q: s2 j: ]7 j$ BHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative% s" x1 T% p8 H# x
clinicaltrials., Q2 K! ]; f% K* K3 G- H
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