LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
' L3 D( P8 T d; D$ ]/ p* D+ WTHERAPE UTIC PERSPECTIVES
* H2 ]; V. z6 t% ?) `4 N; EJ. Mazieres, S. Peters
$ C7 L; k" O3 i* d) \) e1 z$ IIntroduction: 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
- B; e& h( @* Z6 doutcomes 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
& M: I# J+ {* \0 b) Z/ G* \7 Rtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her23 @7 ]8 w( L7 s! X" c
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
! D; y4 I0 F9 y' H' Xand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;, Z" R0 l$ u5 k( \% I" B3 n* P9 j
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for0 L/ c( t2 k, P8 ~$ z% D. m
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
$ W! c# k" K3 g& {; E) x# {lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and, u' H/ G) y" O& R
22.9 months for respectively early stage and stag e IV patients.7 G' g0 [. g% x: D
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,$ x6 o! ^/ t4 o( W/ m8 I
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
) G, z) Q+ Z2 m$ L; tHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
; N- c( X8 z2 Uclinicaltrials.8 @5 o7 w- s$ R( ^, C) _9 R3 s0 v( y
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