LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND4 S- m5 O; P, Q) p7 ~" A3 E# u: W* g& N
THERAPE UTIC PERSPECTIVES
" t! v. B- v5 ~# _1 jJ. Mazieres, S. Peters
2 S! O; a2 K/ e, O8 iIntroduction: 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
4 Z- g* p% F/ qoutcomes 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 targeted5 z+ j* {5 b9 K, t4 `* A& m
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
9 \1 ~& g8 H6 k y- e: htreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
4 z/ Q' b2 ^2 N; u [/ p9 ~& Vand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;+ d& L' A& y1 _) ]
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
0 i% H* Z5 F! t$ ], F. h# p. Otrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
- G: p( ^0 S; `; r" p" @1 zlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
* g8 U5 A w/ K/ G" G1 R. h22.9 months for respectively early stage and stag e IV patients.
' j1 A! v0 O( E/ _4 VConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
; P: M" n& n) U# i9 f; L+ g8 ?! jreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas . y& D: P) K- v, @9 @
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative5 E0 _. P9 u0 L( d
clinicaltrials.
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