LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
7 n0 k d6 I( _% ?THERAPE UTIC PERSPECTIVES4 L2 _! F7 n2 M: z4 A: ]- S/ H
J. Mazieres, S. Peters
3 V/ y# P& X- q2 ^& e. bIntroduction: 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 therapeutic2 r; a" u! E& ?
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
8 J1 T7 b3 |+ Ctreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
+ V+ @5 j6 P& \0 vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations- L* r$ d8 t0 i5 C' J7 ]8 ]2 ?
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
! R+ y) n4 @; U8 m. Ndisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for2 T, Y6 G& v8 S- W" l% K2 p
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to9 E9 S! L* G4 t9 T- \, \* ?
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and- z: v8 x8 D* Z r9 }
22.9 months for respectively early stage and stag e IV patients.- k3 P- |& Z' ~( j a. ?5 |
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,. B; e) X3 B: t; I6 j8 t
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ./ {3 |) L( {3 m4 H4 d' s
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 j! i/ U) E; x1 r+ d
clinicaltrials.- J! E& {4 o& Q4 q7 y
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