LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
2 [: e& K/ O/ r- \; Q- T. TTHERAPE UTIC PERSPECTIVES
4 ^! b' Q+ V4 h H" bJ. Mazieres, S. Peters
# T' @( ?& ~& x; uIntroduction: 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 therapeutic8 Q: e' {! w6 x$ S* f+ s: d; j
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
# D6 n' j- ^( w- z! D! Otreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2. ?' m4 a8 {( F
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
3 G. {9 s+ d0 z; X# L9 y: Band 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;% ?; l! V" A z/ \
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for3 }3 P7 m$ {/ h
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to( G3 { T; Q4 z# b5 q. E: \' A( O
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
5 L- I# c; Z% G6 w5 l22.9 months for respectively early stage and stag e IV patients." t" M4 P8 ^ e3 B. t! a3 a
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,. F& y0 t# e9 c7 u! `
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .* n# I" A3 a% ^# }: M
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative: q4 n4 e8 j1 I8 e
clinicaltrials.
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