LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% M0 ]7 s u4 O: G
THERAPE UTIC PERSPECTIVES
( t/ @: \ N& J1 UJ. Mazieres, S. Peters
4 d3 F+ m0 n9 Z. j/ A8 M. L- wIntroduction: 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 K8 j$ w* e$ c# L) Coutcomes 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 k: a5 d# e1 }( d! }# Wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
% Q! T8 P& h8 P) u) Vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
5 |) H7 m: I5 C; f7 Z: u8 Wand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;9 H: y# H9 a w) n( v
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
2 N/ s( U! `, X. B$ h9 ~9 X5 q, F& r* ctrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to) q X0 N6 z( O& J0 ]/ B
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and- O8 p6 H! w' ^& M* N6 I
22.9 months for respectively early stage and stag e IV patients.
$ w: ]1 d* D' X' e' [( SConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,; t8 H$ r: T& [' [# l, j* \
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .& `, d3 p7 m$ Y3 C3 M3 X
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
) e) d. P1 c7 p2 {3 _clinicaltrials.* e4 N' _5 m/ A& r l/ g
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