LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
( N( V q. @. u9 UTHERAPE UTIC PERSPECTIVES
& T9 ^ J) [1 ~J. Mazieres, S. Peters0 X2 A2 d+ s( H. ~
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( H; k5 X4 ^0 d0 T3 h. T
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
! Q, x! }% [/ `8 u" ~& t+ c# A7 Ytreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2! Y) i$ X% O' y2 D) J& i! p) [6 Q1 A
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
5 Y7 W2 k6 O" \and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;' R! Q X+ n3 }; X2 h
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
8 ?* b' @$ a+ E) N4 [5 Htrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
: J# O0 z$ F8 W5 o) y0 plapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and5 l* a$ G1 Z9 v( |5 A4 R
22.9 months for respectively early stage and stag e IV patients./ ~& L. C2 O; f7 o4 \5 j2 _) a3 ~
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: s5 \( b- E2 Y H: i% j* G
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
' T+ A' |! l% M' d: RHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative3 ?: h% x. n O M7 N
clinicaltrials.
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