LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND( i8 l6 \) j: t; s" j1 q4 o9 _! {+ t
THERAPE UTIC PERSPECTIVES( A+ P3 g7 `9 M5 F1 V) g
J. Mazieres, S. Peters
* G0 L8 u" S" \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 therapeutic1 ] s2 a' Z0 f9 V9 V
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
$ @, X) B. ~& I0 B; r6 H8 W atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2 g) c; t8 K4 B* T9 N
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
* M3 b/ |* M' A% {8 }5 f% Z9 n. mand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;3 |3 M( E# E- l9 \* m! @
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 x* a/ }1 J9 J+ H
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to2 d% l1 [+ L% G' l; L- W' g
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
( N- o4 x$ {) v22.9 months for respectively early stage and stag e IV patients.' }% y' I: `9 ^0 P8 Y
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: j# `: h1 o- b w8 {3 r3 M9 D' i
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
! p, }7 R9 d$ i3 e( QHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
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