LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% a% i/ A4 p3 \. s! n- p; I0 A& s
THERAPE UTIC PERSPECTIVES
. ^# ~$ ?: p. X* R' a8 EJ. Mazieres, S. Peters
2 [; @8 }9 Q. W ZIntroduction: 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
) I4 w4 Y N9 V# C5 R7 S& s/ A; C2 I# `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
3 C5 \# z- g. L0 o7 j, Xtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her28 o5 l; v2 x4 |: V, U& M4 C
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations; V. e3 N* o7 W
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;1 P3 O( P4 p) X7 { J
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for& U4 R6 f$ E* f! G. k" j' B
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
" L {8 L. A% o, N9 N+ J. Zlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and3 j( L; ?/ V+ k. d# R- w! L8 U
22.9 months for respectively early stage and stag e IV patients.
; E R% E) N) I5 h0 J Z) @Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
* r# x( t8 @0 X) W; U) T5 P! greinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .7 B2 Q. W/ V8 e. a K
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative& }$ x0 x. R ^ n2 Y/ _
clinicaltrials.! I# V4 ~5 \& k" {7 J# g
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