LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND; H5 O1 E) T$ F! X7 R6 D
THERAPE UTIC PERSPECTIVES
* f2 p$ B E, ~: Q# O. ^J. Mazieres, S. Peters
- X* Y7 E9 c( l3 v( I* }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 O. B2 I/ s( ], m) O; u9 d
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; t: f/ w$ R$ o+ o
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2 B, \( r/ K+ n; v* q; P2 A1 H" a
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 N( f( i* I6 c% u/ z$ O- D% ]
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
, M) ~+ ~: j, E" o, c% Y7 hdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for- t: y" I" Z2 a3 G4 K- C
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to9 C" n* |/ K& B
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and$ K1 U7 z; d1 y4 c( X3 r8 G k( [: F
22.9 months for respectively early stage and stag e IV patients.
q+ r) f/ {. B5 G1 {Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
! i+ q5 b" F9 `4 ]$ ~9 \# ~reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
* }; W& [% c) l# \+ s! I) JHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
" b9 L6 ]& {* ]! U) _clinicaltrials.
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