LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND0 v1 x* q# l3 s, M7 e
THERAPE UTIC PERSPECTIVES
( Q$ p; N5 E6 j" H! ZJ. Mazieres, S. Peters4 m& M; m( @1 s L- w
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 therapeutic8 r& Z& D r) C# d
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$ C* G' p* t* `1 g! s: H0 b. D$ [. g
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2- [5 E |1 @0 ^2 k
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
\ e0 ~0 e; ^1 N/ \; ~+ Wand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;' A% O+ g- F! k+ J9 |) A6 x
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
1 t. F: X7 d8 e5 ~$ j: \trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
) k& _8 k$ }1 |5 blapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
% z- o1 \5 [: X0 |# n( V/ u22.9 months for respectively early stage and stag e IV patients.
& `3 e' c( ^0 C* h! e2 q* rConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,0 R4 a& b) [, v3 v! Z+ U
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .! ~; _' ?% U8 J0 @. l; P+ ~1 L, j) f
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 x/ b1 ^3 x& aclinicaltrials.
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