LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
) i' v& z8 F; nTHERAPE UTIC PERSPECTIVES
& z$ X9 V' l+ A1 c6 @, yJ. Mazieres, S. Peters
1 H* L6 y3 P" _' O( Y9 ZIntroduction: 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 therapeutic5 a0 N4 M/ h2 s# r. _4 I
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
$ X( g/ e' g: n# \treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2) w# Q5 n6 u/ [2 ]
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
( p* h" b3 n2 ~% Pand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;) G6 X {. n; P- c& z2 E0 v
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 l8 D& l `6 z/ H" w. X
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
! r, ?% M0 _- Ilapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and2 } b' C8 L, K6 e& f
22.9 months for respectively early stage and stag e IV patients.
9 q9 l" D k; J& N' U) dConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,! d6 @: F$ ]2 ]* _
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .0 y& \) Q+ w( @% v$ ?6 |) _
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative' j. ^! k" ^1 K
clinicaltrials.
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