LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
, X$ o2 e/ B0 z; bTHERAPE UTIC PERSPECTIVES
# l7 N! W9 ]/ E# t- J" q+ }J. Mazieres, S. Peters7 ]# ?! R; Z2 m; Z5 \2 X. ?
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 therapeutic6 \% N# ~0 s( R
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 targeted9 n: Z9 B$ f; s- N
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
8 [' x6 R( a/ E; A, O7 Y8 ztreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations" g7 i: n/ C- b% k6 K" p# h$ s
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;6 b% a' @/ Q- m! n- K) a
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for3 _1 y- ]7 w: D; V3 _- C: W4 A5 P3 J
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to$ @+ s& `9 z0 V! _1 p" ~/ c2 k
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
7 a0 R" a. u( J+ P) W22.9 months for respectively early stage and stag e IV patients.* \8 m( w6 _4 l7 Z0 g. J7 C9 c/ H
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,* J9 J8 ^9 A6 Z& ^
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .$ C9 o; o0 N9 Z8 l J) U
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
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