LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND2 R& U+ q1 K5 R" b
THERAPE UTIC PERSPECTIVES
) N) o# a- J- C* r# yJ. Mazieres, S. Peters
2 t% k2 d, `& E1 E* i( |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
0 [7 _# ?8 x9 H0 \# F, v: Loutcomes 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
5 t# y2 \$ e/ ?) Qtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
+ h+ k7 b8 j' utreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations$ ^3 }! X8 a* R! t1 _
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;# L6 l" P6 [3 f. L1 F+ ]
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
/ w# O4 v; h9 V; O( ftrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
; ^% j( \7 }1 xlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
+ j4 G% Q, m1 S8 G* r: C4 H* l22.9 months for respectively early stage and stag e IV patients.
' e( z2 U/ x2 f# A5 m) k: v3 iConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
6 K$ e$ O' t8 y5 V' ]! f4 `) lreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
7 i5 @7 N" o. _* Z( J, \HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 `3 o, P% h6 t+ L: A: i3 z7 {clinicaltrials.5 e. j5 F. W2 F9 z/ t! Q: ^% J
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