LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND, d1 A) U9 D8 B
THERAPE UTIC PERSPECTIVES4 T0 ~& \5 p. h
J. Mazieres, S. Peters
% D. k( }: _2 u$ ?5 fIntroduction: 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
# G+ |% U7 M/ M& w* ]3 G8 ~7 b$ Moutcomes 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* G$ c! J* J8 K# t2 M3 k6 U
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
+ J) [5 v& ^) g) l' D9 Z$ C4 @treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations7 R5 w! \# o2 E$ R- ?# X
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;8 {/ g$ G: H! U2 [; a* t0 Q
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for' |3 @0 C' h' {) @/ ~
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
4 Y" v# d% L' {3 {2 y, @lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
6 B% h9 K, f! h* k; P& T8 X22.9 months for respectively early stage and stag e IV patients.. q( p& R- W6 G4 B$ U7 L2 C) W& r
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
! v' I- k% h$ Q; f" ]6 v3 xreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .6 Q! i k" u0 Z. B8 J
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative8 r2 O$ A! @. _0 u: n+ |5 W( G
clinicaltrials.
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