LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
+ D5 r# }& @, P8 [THERAPE UTIC PERSPECTIVES
. a# A& c4 C$ ], i. ^! ZJ. Mazieres, S. Peters
( X( a1 Z7 v& _) \) B' Y# 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 I: o6 E0 J( d; 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
* M" `5 P: P$ gtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2, B" N3 I8 ~# {$ @. [& k
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations. k2 [% v J) y3 c: N) j
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
/ D) `' b) s$ D: H( j L' `disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for# J W% r% ?! }+ P+ _0 M! }
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to5 X% p6 Y+ Q2 S8 d) h
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and0 X% }$ r% g% B b3 g% [
22.9 months for respectively early stage and stag e IV patients.
. s8 u( c- n8 y! ?4 yConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,3 C* ?* o; h: z/ z/ }0 C4 r
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
; O* j$ ]) Y. |8 j) }5 y, BHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative/ Q' O0 C& a8 s0 k' o8 v
clinicaltrials.
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