LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND2 B& I4 Z1 h+ S& O" ^! \( l" Z
THERAPE UTIC PERSPECTIVES( B! F) @0 f9 W$ R2 ^
J. Mazieres, S. Peters
& \, t' v5 r/ c0 z- a5 i% y7 QIntroduction: 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
y+ r4 z; ~; e) F# c+ 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 targeted
* F& K) h7 V: P$ |: streatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2+ ?* R+ W) I' n. V/ O' F
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
9 I! a: S! ?# G1 E* Rand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: e/ ~! l# \# U9 X. N8 N1 Wdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for% V; y( {5 G, E
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
/ o( @ P, g6 b+ n1 f3 S! P0 Qlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
0 I) V3 F5 ]; m* l' O; e& y4 I22.9 months for respectively early stage and stag e IV patients.
Z$ a: v& j( P- x% k2 kConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,, l0 \+ Q O: Y0 y! O, B4 y/ @
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
! b' w3 \7 y* y3 H( b9 C) A9 RHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
( S% Z' @2 @/ \4 e$ O! n, Hclinicaltrials.0 D$ y: m3 N1 g( S8 l/ ^8 v9 o
|