LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
2 \' B m9 }4 Q- @" g0 uTHERAPE UTIC PERSPECTIVES
1 h9 W* v! Q: e% Z! JJ. Mazieres, S. Peters+ q/ q4 D! g6 W: J/ m2 d+ G' 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+ d# w4 N' [0 Y
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 targeted9 l4 J' {3 ?$ u
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2% }/ V5 s3 u* q( R7 w' X
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations" ~% g' J: s4 h$ n, ~( s" t! N
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
% |8 \5 \) [9 O6 ^( e, D* b: Gdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for- T K, W4 l: t Q# O# P( z
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
* i4 U. ~6 ^ L& A+ |4 [8 F" glapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and2 W) \, A- g/ n6 l
22.9 months for respectively early stage and stag e IV patients.7 D- _9 R8 C# [
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: \' Y% l5 Q# T
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
6 U& V; x& I8 K- c1 e5 pHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative6 R9 |) w# j7 o" B! V; ^+ R
clinicaltrials." S* z2 |3 r5 V) n8 Z7 {/ p+ ^
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