LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND. C# i% o& w2 o6 w
THERAPE UTIC PERSPECTIVES
i6 J# ?. v2 v# l7 _# E* V2 y9 VJ. Mazieres, S. Peters5 L* ?, ^1 r I
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 therapeutic9 i! O: |, N, y
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 targeted3 o; I9 ^$ K2 n% h% `
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2% X( p, K" B- ]# Y/ R
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
. v: Z) o' k) Z. B9 s! }5 x/ Nand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;+ m+ C3 _2 d i
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for( j' c' d8 ^2 h
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to7 |( ^+ p0 L% M8 o" H0 d5 z' Q2 m; Y
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and' [1 R7 t! C( W' u8 V4 {
22.9 months for respectively early stage and stag e IV patients.. y; O7 l# g; e8 Y1 G" @6 H0 t
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
$ L( _- q; P" mreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .* ^+ j7 R# Q, W
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
2 n+ }& p0 e- C0 `* ?! iclinicaltrials.1 }+ w6 l/ B$ c! c6 C- v; o
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