LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
& C- c0 v$ i; m- o5 YTHERAPE UTIC PERSPECTIVES
' D& W+ ` s! B- \% C$ n, s9 v) A: IJ. Mazieres, S. Peters
* g0 b- y8 M+ \) E( @- a/ MIntroduction: 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" b {' D7 d* ]; z5 x% g; b, c
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
- T5 |7 t# e$ N2 x' e( k1 xtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
# L1 z/ Q' I6 l- Y; }1 Otreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
! ?4 W8 K& H: {, [/ K n+ i+ z3 qand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
7 I5 R! u6 [( vdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
6 Y5 I0 |/ @4 q7 Z! ~trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to- `% }; M! D- J2 C+ [
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
( n9 L: f6 t+ w; Y3 f. ~4 v: i22.9 months for respectively early stage and stag e IV patients." |1 F) k! |5 W/ H, p( g+ @
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
1 Q6 Y/ _6 g) g* @# @9 I" c* g9 t preinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ./ o9 {' S* g/ L7 X! o
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative6 j0 n8 H: P S3 b9 ~+ z7 `2 S2 I
clinicaltrials.
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