LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND6 \; H% C# O2 s) j, b4 U
THERAPE UTIC PERSPECTIVES
% ~/ g( c" u% ~* T5 u# pJ. Mazieres, S. Peters7 ^7 C/ S; C7 H5 t8 E
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$ p- J& U9 p4 n6 k1 W
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
4 L, d2 `# R* s' V: c; jtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
& h# U( M+ R- ^treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
" g: [: H! x# W7 j. V: Wand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;$ j% s, Q7 \ w& T
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for7 I7 u1 w2 b, b/ W2 R: i4 m, I" O) {
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to" B' }! w" X! c. T( Z' D ~! N9 O
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and2 {2 f6 `0 n; s
22.9 months for respectively early stage and stag e IV patients.+ i$ m. S' Z" |1 t f0 i
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
0 E9 ^7 q5 j D1 G0 C1 H" Q, Ireinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
9 W. C+ |; M! t$ BHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative( v m5 Z; x5 \) p D
clinicaltrials.
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