LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND( A$ T* i% Y; E6 q
THERAPE UTIC PERSPECTIVES
, f6 y/ J6 J( k' RJ. Mazieres, S. Peters
$ d# D$ _, e+ Q. rIntroduction: 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
$ Q& u/ h) l" J3 ^. @ L- @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
) g, y& w! M4 n4 H. e; Utreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2: ?. G( [5 W/ Y. K3 R
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations) }+ B6 f' t }' N
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
$ t. ^ }* R2 U, Ddisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
0 ^" K( g( a3 `! a6 mtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
& \6 J2 A: e" s. @4 D/ elapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and ]7 \& J7 h. N3 ?+ s0 j4 d5 S
22.9 months for respectively early stage and stag e IV patients./ W# |) X1 g- ~. ]6 O" ?4 k' x; T
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
9 r5 _4 j7 [$ x& X Nreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
$ _. u! h0 M- O3 e, \, M' gHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative) y) A1 y0 ^! K H
clinicaltrials.4 t+ F! N( g. M8 i" H
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