LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
, P$ ]& C' i$ a! j1 d3 e% nTHERAPE UTIC PERSPECTIVES
7 }. i/ N7 p5 Q Y2 j' u. [J. Mazieres, S. Peters& C5 i$ R$ c# A
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( S) B/ w" ^* u
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
6 V; Y1 V: h$ H; s2 o6 k9 {treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
' `' X2 S! w: s* d$ otreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 G( z& O' u$ Z$ A& q/ ~& w
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;3 [9 ~6 E" U. u+ W5 O4 G7 j- G
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for/ \* s% ?! r, v" D9 `
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
9 T, w5 o. `1 E8 D5 s, O0 rlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
6 r2 T* r/ u, j$ h2 G* Q) F- O6 O22.9 months for respectively early stage and stag e IV patients.
0 N- k- r5 v4 |4 d4 i T, LConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,+ X8 e' a' o( d. B; o/ t/ a
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
3 n8 N0 @0 ^1 U, G2 ^; mHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative+ e+ x% l* e2 ]1 c1 k1 o% _
clinicaltrials.( Q$ h) h- |: E' I! S
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