LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
0 \: h& L: ?( L) ]: c8 I6 yTHERAPE UTIC PERSPECTIVES7 z [% X$ Q- U
J. Mazieres, S. Peters
- Z- y& E' V' [% V( v4 F; sIntroduction: 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: ?3 T/ q9 V1 D1 Z) o
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
+ d) k9 `. R/ E* a8 R, Rtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2, F" e3 D' k# j v" n
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
; F8 u5 T$ ?. B7 Y1 V2 Band 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
+ n% |$ I* g9 ^; D. V# d2 T/ C$ Wdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for. q- [' c5 V+ w* {' a4 p
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
- f- G B$ p# v: m* p* q; H* klapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
& a: O0 X% a3 H. a/ O: u22.9 months for respectively early stage and stag e IV patients. T% F& |$ }- B! ~
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,7 K3 G# ]8 c' k- [/ x: q
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 u. \' s0 z6 l P( ?# Y
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
, n3 B5 i' t4 Rclinicaltrials.
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