LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND6 }7 j5 Y9 q2 n m
THERAPE UTIC PERSPECTIVES$ _7 V r$ O- |( ~3 F! ^
J. Mazieres, S. Peters
' y: A& E/ _* j8 e T& B2 ]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+ {! D2 ^- J! [6 p6 T! i/ K& I
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
. N, H2 R; G& W& y5 V1 Jtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
% ^" }% k* d! {$ ]! ntreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations, U5 t) x5 i X$ U' i- K4 \
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;# ~5 s' f6 E C0 N
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for# W! n+ Q' k) p4 s) u4 ?9 N+ g) D0 E
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
1 G' z! e( \5 p$ Z% g( u) s& o0 xlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
. i1 G' u, D7 k# ^22.9 months for respectively early stage and stag e IV patients.
4 ^, v/ C; `( v6 Y2 eConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,6 K6 U$ s+ ?: x) N
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
4 T" ?* l N; I7 G& K4 EHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
, J- d+ h A( X0 M3 ?clinicaltrials.
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