LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND/ O+ m- J6 z& h3 G1 t' Q! q2 E
THERAPE UTIC PERSPECTIVES
9 l* E7 l* c% k6 A, [# E) ~J. Mazieres, S. Peters
: N$ Z- R" Q! 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 therapeutic: R1 `# ^" Q' W* l
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) @- B$ U1 B
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
9 |3 a, Q( z: I9 K Qtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations6 K; V6 Y* c1 A! V! b
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
$ Z# s. D, ?8 c2 cdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 q# P- e# i8 x D0 m% m
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to$ Q7 W0 E+ V3 D' F8 j W
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and- f% k0 B6 l, }& C
22.9 months for respectively early stage and stag e IV patients.
/ p! Z, p2 l; o$ J3 K+ N+ eConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,& X; R/ G: Y! c# U& e U
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
, z5 l+ w; Q+ Z6 Y. p" z$ p8 ZHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative- l. j+ u* ]" r; S( e
clinicaltrials.
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