LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
4 t4 g' g9 p( C2 m( f/ fTHERAPE UTIC PERSPECTIVES0 B. a/ O r4 z1 z( {3 k+ C
J. Mazieres, S. Peters
; G0 y5 b+ B" PIntroduction: 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- M8 }8 @3 v+ G
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
$ f2 f' k" G' E3 V" Y5 Ltreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her29 u7 a v3 l( j2 H
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
0 n& Q( e( \0 b6 K* y6 _9 I& Dand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;- i+ Q% ?8 X3 ]; y7 m z; L! O
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for1 \6 p w- @- }* L) P) S
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to" |: H& B% a2 w1 g* v& I2 U
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and& H& D% d9 t7 c* \8 s# G
22.9 months for respectively early stage and stag e IV patients., S" \) _ `6 `
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,- m/ E% s0 [" H; _
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 e! e N. h& g: }1 s. D
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative$ g! F5 c0 q; D4 e/ h
clinicaltrials.
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