LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND! E3 _: u4 F0 q5 C
THERAPE UTIC PERSPECTIVES
' c0 K+ Z" ]9 o0 j" D4 S6 D# E* O7 [J. Mazieres, S. Peters
1 `& c1 h J" b0 jIntroduction: 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
, _/ g% g1 J: [/ H9 doutcomes 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
( F7 B6 S4 o% T0 ktreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
4 X" W1 I3 \: a8 r: K6 P/ a! ttreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
$ C! m" Q! O5 Pand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;; o' I, v6 r( j, t) u. k) f
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for. O6 u7 @# e+ Y) I" H) {; |8 \
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
% F& F. F6 P1 z6 \3 E+ `lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and4 T7 C9 c* _( K! A
22.9 months for respectively early stage and stag e IV patients., | U% t' w# P- Y) n3 A
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
/ C& P5 S* k& ~reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .( K" \# `: g9 [# a8 m$ U; U( ?
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
* A y/ N x# `, f. b: B* cclinicaltrials.
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