LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
" Y& S0 N6 m; o# RTHERAPE UTIC PERSPECTIVES
( v, D6 E, I: {6 WJ. Mazieres, S. Peters
; C4 o/ C! ?5 wIntroduction: 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
! g( k8 q' }* L, c, loutcomes 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
2 \4 {) Q! A$ ^; Z6 ], ptreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
& h+ D4 f+ ]0 c$ U1 `) @: L% Ttreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations( E8 ?1 V) r+ i: _, ~
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;% `9 _) U7 H! z4 X
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for' S' y2 b' B) m* m0 C- K( u) ~
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
3 v( E2 ?1 g) Flapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and& F. V& m0 c1 g8 y
22.9 months for respectively early stage and stag e IV patients.% F" T; i1 t# i' s' ~
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,! V% a/ ]( `$ c! x) ?6 N
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ., ^$ b \* _, h' q3 ]- U# s0 k/ @
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
0 g5 a4 v4 O. P+ A6 F' Z, l: Pclinicaltrials.& x1 }) u" N8 y! u1 Y4 j: Q) q* h! d7 ?
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