LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND: L5 A, P2 e" C; j* f* K
THERAPE UTIC PERSPECTIVES
3 k6 L) i0 e- H/ ^. ZJ. Mazieres, S. Peters
7 m! U. y% X9 C2 V8 J) i: AIntroduction: 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
3 K/ a5 d) j" v# F6 foutcomes 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& y$ k! @' m) b2 K7 ?5 _: T
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
' N* D$ J" C) O- f+ s9 ltreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
; }4 ]2 H V8 a3 p4 q6 Yand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;+ H A! ]& V. X7 K7 e' D: r v+ i
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
Z4 g# C3 ?* [1 M/ n: A1 R0 ltrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to3 @- W% p y. D9 O. k8 [
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
# {# ]4 I4 N3 F0 O9 a; B22.9 months for respectively early stage and stag e IV patients.; j( [& H; ^3 G0 i
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 _1 x( k5 @3 P5 p& {/ }8 j" l; Qreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
2 n( R4 U5 c. K% t/ q0 KHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative) P9 F3 k5 T6 c, o) g% e |
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