LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
* ?) |# a) Q7 yTHERAPE UTIC PERSPECTIVES
) d" ?3 t5 ~# N. m* }' ]J. Mazieres, S. Peters
$ M3 V$ k' m0 V. x* AIntroduction: 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( @! [1 R" M" U' S
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
8 {+ v+ h2 E' D" ctreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her26 @5 |+ q% `# W( P q' t( z" q
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
- A8 x* Q7 Q* s% Jand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;# Z5 Y5 R- c/ F, X$ R; u
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
" o. ?+ h, r( R! f4 A1 Utrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to+ ~6 D/ M0 }: _" n Z ` z
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
( ^/ r5 y" i" b/ e# T9 r/ B! H22.9 months for respectively early stage and stag e IV patients.
' w' O& T. Z- m( yConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 g. G: j: d6 L4 M& N) Xreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
8 M; C% h/ M) Z3 h3 X+ QHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
9 R: ?& w C5 X! k& z& ]clinicaltrials.* D6 S3 i; ^: U( Y& s% G( k2 E% j
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