LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND( {4 C$ u& M6 ^ K& g
THERAPE UTIC PERSPECTIVES: A' G* F6 \1 x1 r7 w
J. Mazieres, S. Peters4 s# ^& g" Y' V
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
! d H: N& x/ t4 v, l7 noutcomes 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
7 W: @# e; y+ r3 Jtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2/ {8 h; e8 I" e0 x9 \
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 G8 \5 K% B9 ~& ~- b) b, c
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: V9 g. X% c3 r0 Ydisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for# E: U' p" K1 a0 q$ E
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
2 v+ L2 g- Z' T. _) alapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
: d) L% M7 R; i- e' d+ c22.9 months for respectively early stage and stag e IV patients.
6 B7 N" G' J+ nConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: _7 q8 h1 b1 Y T* }% D
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .+ h# s4 p$ }" h9 e& v2 ~8 X
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
* ?1 h4 ~6 z5 I7 Mclinicaltrials.( m/ w" T! X5 E+ X7 N) C* e
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