LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
3 j c3 U) s8 GTHERAPE UTIC PERSPECTIVES
8 u& L4 Z/ X4 m, i( l3 IJ. Mazieres, S. Peters
6 c- H- i' N6 V0 bIntroduction: 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 therapeutic0 F$ F [! ]' B) d/ M& S
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" S, r C+ u4 Z, Q) ~treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her23 e, w8 q! |' | W
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations% N6 W I. A* j$ k3 z$ w
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;" o+ @, _( t) u! u/ c$ Q
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for1 b! J0 E6 {2 }1 u. b
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
' x, B- [: c; k; G) l ]+ k- vlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
! o; I7 O1 J, Z' p' l; f. e22.9 months for respectively early stage and stag e IV patients./ a* a& _& Q& d& x
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,9 w! x7 f7 E; `* ]2 C( {* W0 B
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. q! Y- k" [; u2 x6 e# Q/ V5 x4 ?HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative# ?" ]: u+ O* Y0 ~. O
clinicaltrials.. ]5 ]0 a& M9 c3 M* y: [ g
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