LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
! }& a6 W: S) }$ HTHERAPE UTIC PERSPECTIVES
: @' g" C$ n- N* r0 |J. Mazieres, S. Peters
- c7 m. d; N$ S) _! q: j fIntroduction: 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
( c2 D/ v9 N& C* B! }& }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$ B# V# ?1 k d1 e! R
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
: n8 N6 N) Z5 s! \1 q; j( _treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
4 ?9 M, ^4 K+ ]4 xand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
1 O* Z6 X" E. ]disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
% ~- d; u& b1 e, [. Wtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
+ h- s0 ~ V( S! n1 b8 \& Plapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
3 Y* R* Z5 f2 {22.9 months for respectively early stage and stag e IV patients./ f5 n) r, G) g5 ^% e4 d( k
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
4 y2 d+ \0 R; T) `4 {: n: y; Jreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .7 p0 v* W& M5 Y& f4 X5 x
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
2 t9 m% [" B6 e# j0 dclinicaltrials.+ @9 ?9 M- V, w2 }- y" ]: f! @+ ~
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