LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
" ^: _3 n9 `; i- o' y. i* QTHERAPE UTIC PERSPECTIVES
$ Q8 e" B! L+ v$ W4 GJ. Mazieres, S. Peters
2 r) w: d7 c4 U9 w+ t1 dIntroduction: 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
6 L; i7 B% g% {4 @, qoutcomes 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 M# K$ u$ k/ t) R* B% A$ ctreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
* |2 z2 W1 q2 t+ Y. b$ e% p; Vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
" G1 w8 j0 ^7 o6 h6 A0 Jand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
( {7 G3 ?1 `2 ]2 ?1 D' T/ Idisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
* `! M' g8 P1 w2 P$ h6 Xtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to6 @8 R+ S* M: } N) Z1 f* O
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
8 r2 o4 z5 d6 Z4 H6 L. D7 G- s22.9 months for respectively early stage and stag e IV patients.
4 _% F1 O- G# a& z3 A. ?, p3 Q6 ^* [$ RConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
! L' M& C) X# G, X. C3 B6 \reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .! d: |6 r X; M# C; v* ^
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative4 ?+ ^3 m/ A, z" T9 D# b7 ~2 A
clinicaltrials./ y. {/ M& r, E9 o4 z" W
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