LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND# K' {. A5 P& j, i* M9 X
THERAPE UTIC PERSPECTIVES
4 O0 m+ P3 D$ D9 FJ. Mazieres, S. Peters
) O2 c% ~& \9 K% gIntroduction: 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
- r) w* [' h* D- Z# k* @5 ooutcomes 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
# ~* d- q- e% @! y$ y* wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2/ ?- V+ L; A8 ^+ m& f% I: F
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations/ b9 `5 s/ M4 B1 x; z3 r
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
, e$ E, _+ e! E6 Kdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
7 L) I2 W0 k# m" X+ J B1 Jtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
9 @/ C* ^, z& ]' B7 Olapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and8 D: b* R' T5 E# V3 M
22.9 months for respectively early stage and stag e IV patients.9 N$ k8 V4 I1 b" O7 M6 }
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
% g9 U4 l4 S7 p* t, B- P' Jreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .2 u; I. o% C# L0 `
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
. S& K4 o. [1 ?clinicaltrials.
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