LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
0 D8 W9 x# Q% ITHERAPE UTIC PERSPECTIVES7 Y6 I2 W9 R+ ? l1 O
J. Mazieres, S. Peters
6 ^% _, [: K, kIntroduction: 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, X3 M: [3 B- T7 p; y
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
! P' l! N: b, C- K6 Q4 b$ y- ptreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
2 \% K( f& s2 e4 a# }0 k4 j* [/ R4 ytreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations0 I" z6 X- ?! d2 Y. u! S. Z0 e0 N! G& @
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: G+ }! r" Y9 tdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
7 s2 O+ U& B( \% ^9 Ftrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
, L1 a+ F3 v, @1 i0 t' Z; L' rlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
- [3 u4 V6 d3 A: D0 a22.9 months for respectively early stage and stag e IV patients.
$ P' y0 b7 X! @3 |. X/ MConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
1 K' V, h. A' S6 Qreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
" x; S7 x8 q" RHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative% O5 B' U+ Z6 {1 `: _. G) z
clinicaltrials.
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