LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
: O# V6 R! v8 Y% V- zTHERAPE UTIC PERSPECTIVES8 C4 i. [! d: c4 ^& M; ^! e* ]
J. Mazieres, S. Peters4 s, f3 h+ M# q* z1 r, P, _( N
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 therapeutic3 o6 V1 F. y, B; p
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
- y# f# Y+ z8 H- ]% T9 Vtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
: j" q4 t& |7 Z/ Y) x E( ctreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations, u7 a2 \' ?, |$ I: p3 P
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;3 c- g/ q1 j1 J$ t7 Q
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for- _' c& `2 s* N4 a& t0 `6 y& _
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
% W( g: ~0 p8 t" ]* L/ `) ylapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
- ^# l& z1 ^' I- |0 p22.9 months for respectively early stage and stag e IV patients.3 z" M9 h1 F. A
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
( x9 B( }" h3 ?6 Qreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .1 Z8 B/ e' |9 \+ Q/ h9 I
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
U7 z5 C" j& \clinicaltrials.
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