LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND. q- Y# Q- L. h+ t5 ~1 c$ M# M
THERAPE UTIC PERSPECTIVES2 D3 ?) n0 f* v
J. Mazieres, S. Peters8 h. S& L+ a* z* {5 ]- M" q' Y
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 therapeutic
0 k+ c* Z: y- i# Moutcomes 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
% N+ V; J5 f3 V8 x) `0 N) U. O7 Vtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
5 T( K1 j4 v2 M2 D" K) V9 z& Rtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations; s* S ]. J/ J+ l' `
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
9 Y* D, H2 g* Xdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for" N: Z2 o7 {$ E. Q& [1 y% E2 R1 M
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to) P/ |; Z! E2 Q1 O5 `
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
4 R. Z, F/ ~* P6 c; K1 N& B22.9 months for respectively early stage and stag e IV patients.; j! f7 l, D) f* A7 l2 o. u) D7 B7 p
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
; X4 s& ?4 |3 breinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
' H/ \! I" e, A) a6 ]2 ]" ~HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative( ?; C+ W$ P* |9 u. A2 N! G Q
clinicaltrials.
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