LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
7 ?. Q- f& ?! t" BTHERAPE UTIC PERSPECTIVES
- W5 @, e& {1 S0 i. WJ. Mazieres, S. Peters# u6 E6 l. k, E( ^
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
. c1 `9 t1 [- X `1 Boutcomes 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
2 F9 ?, a+ @# G2 J# `treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2" m6 T; U% L, ~* w% l( z3 r
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations2 M/ F3 X: ~( J, }
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
- F+ T3 o& |9 c. ~, z' \( [disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for+ t4 K( O5 Q! d! T& n8 P! W, e- h
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
- _) K( L4 v9 G. H7 @# R: [- ulapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
7 H/ e. o% N* @5 m* H1 o- Y22.9 months for respectively early stage and stag e IV patients.
1 Y- x" p% d% V3 j0 s" q/ MConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,/ o+ r. E6 P* T2 o) n
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 T# d" H a' U% {
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative0 R. m2 ?1 o' ?7 U+ g9 A
clinicaltrials.
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