LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 k% W) |4 c9 b) f
THERAPE UTIC PERSPECTIVES
* p" I- K! O. e. a. n2 g4 I1 f" L6 _, tJ. Mazieres, S. Peters- D& b4 r4 H) c/ ~( s; w+ Q) B
Introduction: 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 therapeutic5 P% U/ D* `8 z* ^4 t4 l
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 targeted9 Y9 f( }! d4 ~# O
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
, X1 v4 Q: C0 itreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations1 a" @) h% N+ ~5 p! C r: U
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
* _ I5 r0 K/ V* ^# t/ T& _disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for ~# f$ z2 r; f6 @, i! g
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
- @5 L% w) t7 y Q2 blapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
: v( ?" d# N* X5 {2 l% \22.9 months for respectively early stage and stag e IV patients.
8 J' {3 _4 v" V! B+ uConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
' r5 p' @7 j" m3 k+ ]; ureinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .9 A6 ~4 K' [( F: d
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 \. W9 a$ O2 U/ c$ U, q6 ]
clinicaltrials.$ Q! w" ` e2 u
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