LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND' `0 u0 E5 N6 S; q% L
THERAPE UTIC PERSPECTIVES
1 F+ v& o4 z5 @, BJ. Mazieres, S. Peters' p- X, Q7 a/ Y6 a6 P" m
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: ^9 f0 W( b/ @+ B2 `4 z( z( W2 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
: }9 Y4 e- L0 h, C; `0 Ztreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
8 b% h& ^/ d5 e! jtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations/ K0 A3 C* X0 X3 e) `
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
6 L5 ?7 K/ g( R* f+ i3 Z# edisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
3 I5 I! T C3 ]5 [; Ntrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
; k9 D- V6 e5 l" ^# k) x7 q3 _lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and" w, a' R" E' }0 M+ G" B% c
22.9 months for respectively early stage and stag e IV patients.0 L; ^6 B ^: \8 Z# H% |4 k' m! L
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
# G: d- z! Z1 J% @# _reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. c8 y2 t7 @2 GHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative |6 @+ I7 I; Y% A. E! N
clinicaltrials.# N. F% E' I1 l, o
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