LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 j' t3 K g! O2 j5 f
THERAPE UTIC PERSPECTIVES ~0 c0 w) \5 {# I' k' y
J. Mazieres, S. Peters
/ T- ^! U/ {7 i$ t! p4 C9 Q+ VIntroduction: 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
2 C" l7 I: ^$ i0 R% Ioutcomes 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
/ {9 o+ m3 t; T& }" Ptreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2: v( H; n# W2 X' \1 B# g5 U6 E+ Q
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations6 j a% X1 V4 q% }# d3 }/ k7 z9 \, K
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;/ @: J0 b% }% | Q1 ]* t* {9 B
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
6 R0 P2 A$ Q7 u6 m' P# I: etrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
( A- [8 `8 z% m1 X c6 D* Ilapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
& S) V; | I& {9 L) M/ s7 `+ {( z22.9 months for respectively early stage and stag e IV patients.$ }& K7 `: N) `9 }$ n& G Z
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
, u$ h8 ^. i: B" Kreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ." }% f% w! l: p" h7 C
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative9 p7 J0 n# p y4 _0 v
clinicaltrials.; U; [( [2 |2 d
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