LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% u! _) }9 r* Y' m' B4 a6 U
THERAPE UTIC PERSPECTIVES
( _ |7 J t4 ~8 p2 Z: W8 kJ. Mazieres, S. Peters. a8 T6 L0 F( A E" D& O# c' G
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 therapeutic
! Q$ U# s I6 ~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: x7 T5 b; w1 Q0 ]- T2 X9 {
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
) N/ [/ K; Q& L! q+ Otreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations/ t( ?( I8 ~4 p8 r3 y3 Q- z
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;' i% Q# P! P- _! a
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
: t; t7 x6 T) n" V" S! D6 Wtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to& G* ?) Q( |( l* }! j
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and# O: w* Q4 c2 m/ p7 R& O8 ~9 q6 T
22.9 months for respectively early stage and stag e IV patients.- g/ X! F# M* t( Q$ K
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
8 i+ E1 \$ x/ L8 w3 N* w2 u" Z0 [reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
! D- z+ U" @6 ]; k! W% NHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative" v- ?" x( a' b( m- e
clinicaltrials.1 |! A o# `1 |! f$ I4 ~; X
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