LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
2 O) U% k7 [4 x5 oTHERAPE UTIC PERSPECTIVES9 C# t0 J0 J* _4 S7 {( B f2 B
J. Mazieres, S. Peters4 |& Y; f" P ]" h+ 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
" M) X; L. H% `+ t& a5 p+ ?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 i, ^9 @- a9 c% _: h; m
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her22 ~0 m4 j/ r" j& P4 K9 ?
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations8 l: |( H/ M9 Z; P
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
( x' c, @! ?3 E4 G; A; pdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
* k3 ^, a% h1 C, M" J' Ctrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
# c6 T w1 v7 | n1 w9 zlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
2 A# b' i. d5 }* z( y+ R22.9 months for respectively early stage and stag e IV patients.
, U& K8 l; S" B* K/ o$ n2 DConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
1 j5 u5 Z% h% K* v* creinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .0 |7 ]8 ~; ]7 w8 `4 J5 q
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative4 x) e# x$ v6 `- s
clinicaltrials.
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