LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND* f$ a+ V$ T( ~( u( }
THERAPE UTIC PERSPECTIVES; d4 x6 s- B& A' k. s2 I
J. Mazieres, S. Peters
% W b- a7 }/ ^3 N; ]4 P/ xIntroduction: 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
4 s+ Q$ o+ V! g4 w% Aoutcomes 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
1 q( S5 D/ V% z# x5 f, \$ wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
d+ p5 s& D# J! x. ]0 [0 ptreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
* g/ M, b$ Z4 b* cand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;0 A5 h$ r3 H$ V1 Y$ H9 v. C) q4 w
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
& g- K/ C* m) V o) utrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
1 B8 a9 l1 j9 u) t7 @; qlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and ^% X1 T' t" a- x$ [$ _" |2 M2 O# O
22.9 months for respectively early stage and stag e IV patients." [* h+ i+ g& I* i# {/ w
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,' X/ Y6 ^0 g! L* p! l D& j! H) B* J
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
$ \- }" E' N8 ?! {HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
1 h- `7 U% `3 m% a# iclinicaltrials.
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