LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND" x; U# t' y. n" [; W
THERAPE UTIC PERSPECTIVES5 t% u( r+ I/ a8 t6 a0 k3 n
J. Mazieres, S. Peters
% G! Q7 B! u8 k( F8 M$ i. d8 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
* `* p3 Q4 d l5 f; y/ Y6 R! Toutcomes 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
6 }4 l5 o; F5 x1 Rtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2% n/ ^# `( u5 z/ m+ C' `" k
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
" f( A$ W d- U7 Q. |and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;. b$ h5 M9 L. Y' i$ A- X
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for6 j8 s7 Q. h" Q0 z a
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
% _5 V. D, X" G$ o. q! \5 l) Mlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and3 C; _) C7 u0 c" w
22.9 months for respectively early stage and stag e IV patients.2 t1 R1 O% k7 v" a2 L1 {2 G4 x
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,0 t0 @( t3 V$ w4 w
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .% o8 M) s8 H* B9 L9 U. Q' J7 k
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 x% u) o# t/ A) u- @8 j# D+ Y
clinicaltrials.3 n$ C: I; l& f h/ ^
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