LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
" P- t' {1 `7 O3 s, M0 mTHERAPE UTIC PERSPECTIVES# w" s7 _( V) b" P# W1 @
J. Mazieres, S. Peters
) |' ~* b. @. `4 J9 {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
; `: ]/ z; {: s9 p% J7 [$ n6 \" houtcomes 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
7 ?. J4 S& s9 W8 J! {8 L" ?" Ntreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2; b0 Z) W7 i R" I' k1 X% H9 L
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
) k/ k) C ]- \# c/ Wand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;7 v: M$ |8 q8 t K
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for# v6 o: B" ^1 e! k: n6 K9 T
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to) n+ m4 F; M- b& g
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
1 E9 ^+ v, L" F" T4 }22.9 months for respectively early stage and stag e IV patients.+ t6 ~- o1 d3 q7 [& P* J5 `, e
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
" { u. [# A3 Treinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .% w. I+ f2 Q' p
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative: J, v( q+ E, \' D; v
clinicaltrials.; Y( u0 h1 X! s
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