LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND8 k6 R P: ^4 q# S
THERAPE UTIC PERSPECTIVES
/ v6 `; j9 X9 C$ FJ. Mazieres, S. Peters% f) A% E9 ^, E, l+ I5 G5 l+ h8 c
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
! m4 _: B: C# D/ J. youtcomes 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, @4 o/ T/ \ c. [: m+ E7 m4 Q$ l
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
. @7 x6 S$ { ? }" |treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
6 C& j% Z3 Z- g- r+ j) sand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;& R" S$ ^, E! {" S! p
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for a; e. C" z& C6 p6 R( {- L
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to/ `- D9 a% U1 H4 c% W
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and" K9 \0 d! l" z! @ g3 r
22.9 months for respectively early stage and stag e IV patients.
I2 M. W8 }# S, e% PConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 V7 t8 w$ Q6 H0 Q9 c$ m. y0 Dreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .4 i, L: }: p& r' _
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative! ]; n+ F" v' y; v, ^: a; J6 M
clinicaltrials.
$ v0 e b* j- Q |