LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
& \1 L+ i/ Q' ^6 Q8 iTHERAPE UTIC PERSPECTIVES
! Y. l7 R o9 {4 TJ. Mazieres, S. Peters" x- ?# V. k- z
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
6 N- U- S. @3 ]9 f) ?: c" aoutcomes 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; `" V) y) W* T5 J' f, ?0 i
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2: g) ?( p9 W1 J" E1 t& v Z
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
" {2 C: J: B. x& U, dand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
5 N' |, Z/ c' |- E9 k% K' wdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for' ^' v2 B0 Y& i: ^* L( j# Y
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
8 F0 Z' W4 G( M) Slapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
4 h! C3 f$ |2 E5 g4 b22.9 months for respectively early stage and stag e IV patients.
4 Q0 N N+ Y9 d+ b- FConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
0 @* h/ Z! O* D: L+ ireinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .$ O1 ~& g- N7 R4 [0 u
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative% t6 {7 W& C2 M V/ _% T
clinicaltrials.$ @( S6 E. ~' t# n0 n# n
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