LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND# r6 S! ~' Y D9 O1 H
THERAPE UTIC PERSPECTIVES
7 @1 S- `: L* n) b6 u) X# FJ. Mazieres, S. Peters
" ]) {% I6 i. C) n( `$ jIntroduction: 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
4 G; i5 c. B8 {0 V, M/ r! voutcomes 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 targeted7 O% n" `) Q- d5 X1 G
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
3 o2 ~! l7 T* u2 @: Rtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations k3 E6 i% m9 S" o6 G
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;% s2 ~1 N3 g& F3 j4 {
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
4 F# J1 j/ J7 h5 Q o/ v, jtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to) Q1 j; y: z) d% p; s4 o- g
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
4 f4 U; x- @+ v22.9 months for respectively early stage and stag e IV patients.
/ o# b/ H; X* n7 m% i& r1 j YConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,6 ` ?; C: \9 J$ w' O3 O4 x
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
1 H) S6 b# Y5 D2 d4 J* w4 zHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
& K4 W# [; X6 g/ Q7 pclinicaltrials.
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