LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
/ ]& C) U* f2 B. ]7 A5 f+ ^+ ITHERAPE UTIC PERSPECTIVES
5 l3 [8 W G3 x5 I6 |- vJ. Mazieres, S. Peters
7 C% `! C4 V2 @8 N" @9 _2 Z8 [: CIntroduction: 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
: a/ F5 y2 y1 i( j* N4 r/ ~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+ k- D" x/ Q% ], y. C0 v; z
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
$ U7 h2 R1 y' h. ?( r( o: utreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 A! y! G9 }) m5 z
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;+ [. z( y: N7 p; [! Z* ^
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for& t x- D- G4 A
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to5 p( W) K) t8 x* Y
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
' j0 l- B7 F8 e" w+ z0 A+ b7 z- b22.9 months for respectively early stage and stag e IV patients.
0 x; z. s6 {, U7 x, [1 r2 AConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
0 ~; K- w/ u& f' S1 xreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .% i s3 J& O, {6 h+ \1 H
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative& t4 D6 \: O/ f/ q! P
clinicaltrials.
) m/ T% l9 G% y' a4 V+ |0 y |