LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND4 B, L" Y; i( r# O) r$ A9 M: A
THERAPE UTIC PERSPECTIVES
# m) {4 w1 k: w% RJ. Mazieres, S. Peters
+ S4 T: r" x; 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
9 J6 \' |4 ]- j/ @; v" G1 y: k+ Youtcomes 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
" j# O# f5 y0 ~& Z$ l+ Rtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her20 `8 j) [2 f+ i I$ Z3 N: n
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
3 e+ O1 D) \; p* @# Iand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
; b k5 W( V# X, O# ndisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for. {! H" p# |: i% ^- J6 N
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
8 F8 q2 s( V: g( s7 ]1 S8 }1 Zlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
$ m6 B( [, ~7 H0 }4 K* Z1 n22.9 months for respectively early stage and stag e IV patients.
% a4 @7 G. C5 |. jConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
) s! {2 t F Q9 L+ Breinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .' ^: ]/ B6 M; j
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
* o& I5 k" D. ?. hclinicaltrials." V1 [* E) r# w( K! b
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