LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
$ ^8 K$ W3 [: q0 C: |' h) QTHERAPE UTIC PERSPECTIVES1 e& _: n( a# P/ o# {, j$ D: B* t
J. Mazieres, S. Peters* H7 B: L5 P" \% G. D
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; o( q0 _# {7 O/ N G( U3 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 N% ^: W/ @" h1 n) c4 I* s1 H" T
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2; S/ i4 m- B2 x/ z' B( S1 M
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations, x& ?! M* |4 W* B3 T
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
2 M& P- q" x5 P+ O$ xdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
& n9 S8 {8 a: M. \; n4 e* L8 S4 Xtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
5 ]9 Z8 T& ~. T D: a1 y: i- |lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
& |$ m9 z7 r; A" j0 K22.9 months for respectively early stage and stag e IV patients.
* Y" {/ i6 H9 q3 R oConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
" J8 y2 r7 z3 r3 H) {reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .6 Y) T$ E7 ~- h% f7 d
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
, K ?) ]5 _8 p: e/ \clinicaltrials.
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