LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND X% \+ T' v6 T# W, o) ~: e
THERAPE UTIC PERSPECTIVES
8 @& }/ ] M& _% N8 T0 H% xJ. Mazieres, S. Peters
9 S7 s" z5 ~2 c/ F- jIntroduction: 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 s5 B# f2 T) N$ v4 [
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 v/ U* F, J; H, `, U% u; G. Q
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2. V0 L4 r0 u2 `! b2 V" P
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations( p1 c8 Y0 O6 [9 y# t
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;, c+ h; j8 X5 C* y! W
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
# b+ T7 @6 x- A9 ttrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
5 K" p. }. b" }' k( v! Ulapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
0 ~4 f; p/ v5 Q22.9 months for respectively early stage and stag e IV patients.- }3 ^9 M. |: W1 K
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,. A! ~! V4 c# k' n! o$ }. t g
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 p3 g! N' B+ k1 W9 D2 }6 h7 Q
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative4 Q8 v# m9 g- S, T0 P$ l! W. s- ]$ i
clinicaltrials.
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