LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND6 y" d2 k/ _8 x, S. S
THERAPE UTIC PERSPECTIVES
& ~" ~! H3 @- t* U) EJ. Mazieres, S. Peters+ s) q% M: h7 j
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
! g1 n6 `. c7 m+ j: I7 foutcomes 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
% ]! e6 q3 r/ l2 M; y$ D; C' atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
6 W6 u* U* R2 G9 B5 _) M* }' gtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations) F8 Q% R. O) {7 e5 s
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
0 r' M; a/ r5 ?" ~8 Q: @disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 m5 T4 B/ A6 [
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to: Z6 x% `0 y' R) f) s0 ~" M
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and. ]/ r1 d8 G2 `1 E! [3 @4 _* W- t. m
22.9 months for respectively early stage and stag e IV patients.
: F& ?9 g! i) b: p* a2 k/ ~Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
* w; d: h- { ~! _3 T2 e, e: |reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ./ |- t( r/ w' X# H5 K' l7 c2 ^; w( I
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative) }7 X: d9 U. W( C" O4 X+ y3 a
clinicaltrials. S4 a O% H, m8 {' u# [9 a
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