LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND! b& J$ Y7 v: n4 ^' i
THERAPE UTIC PERSPECTIVES
; t( G) Y9 ?' J% V. YJ. Mazieres, S. Peters) v3 I4 C8 o {8 W
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; J2 i8 V! d! s7 {7 l0 e/ J
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
0 s# i) C& b9 C! t' [; etreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
! _9 C7 S: n+ \! Z E Ztreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
0 R" C5 Z0 d7 \- land 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
1 p; `9 ^8 E: S G6 ]disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
0 p! X, E/ s4 ]# I1 Htrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to, V( E* g" Z S+ w4 U
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and" `$ D% [- X' }' O1 ~
22.9 months for respectively early stage and stag e IV patients.! O! r1 T3 K p% _
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
* X. k, T2 D% S/ `* H% xreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .2 g; k% N3 {- y/ I0 l
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative8 u1 h- o: j# M% I. V
clinicaltrials.
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