LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND, i! x% ~ `; ~: P m2 }
THERAPE UTIC PERSPECTIVES
- G1 Z; t Z. G1 Y4 ~: }J. Mazieres, S. Peters
! A! W) s" }. @" T; YIntroduction: 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+ G2 x3 t3 }( g- ]3 ~4 ?! L3 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
' B% p6 Y# y) j: otreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her25 w& E j) Z3 g
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
& s8 s/ ]: c8 ~! ^. K9 u& Z% band 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;/ x! G- {) V; h+ v) `
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
9 R6 |7 H* b. _( Btrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to+ [. q3 k4 x1 h8 U
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
& E( W( S2 ^& O: |$ N, Y% f22.9 months for respectively early stage and stag e IV patients.
! N& m% N/ S. a0 Y" gConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 p, \1 g" c8 H5 Preinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .% ]3 z( H3 Q0 m$ w& G8 Q
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 Q2 ?0 R$ C% k5 o% p8 e8 h
clinicaltrials.4 o1 G% z+ ~$ W* Q+ z
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