LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND$ O2 u7 U' R# X% n
THERAPE UTIC PERSPECTIVES
$ [! v* Q4 O% |J. Mazieres, S. Peters
7 ?) f+ A7 R5 \, U( |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: Y7 b/ V0 Y+ @+ A
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 r% r8 e+ a r. D( b
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
$ X: v- Y6 i5 Atreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
3 {! r. a* B. T! J0 qand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
3 N) y9 A" ?/ l5 e) Qdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 Z6 ^6 {+ c; g8 G& c9 i. c
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
2 Q3 d* m3 y6 D. D& ?& E" o" Dlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
. F! m8 L0 F7 C! ?/ C% O: f/ N22.9 months for respectively early stage and stag e IV patients.! v \9 H* M- \# H4 w) c" u9 F
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,0 J/ Y3 C: o( H; J3 E9 E
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
% z5 L( C+ a& ?( ]+ a' RHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 M% l$ N; D W& K% iclinicaltrials.% i- B, R2 ?' m
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