LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
: s2 L* g5 T8 t- W, gTHERAPE UTIC PERSPECTIVES
2 }# [3 _3 R3 m2 nJ. Mazieres, S. Peters& M+ J# s! z+ o! Z4 k
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
; S1 t9 O, }& N; @8 l6 O- Goutcomes 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- y/ {6 g- I+ o. B' l- ]
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
o8 p4 r9 h/ S7 N' N- T9 ftreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
+ F3 E! U# v% C( Rand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;$ w; l8 F! ^/ S; N* J k b; {
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
* v4 S8 {* R- F' S7 V$ ytrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to/ O+ K/ @2 R$ m. d
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and) z+ M/ i( @& u9 i4 P/ |, V: V
22.9 months for respectively early stage and stag e IV patients.* h2 `. r" Y7 x9 B( E' q
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
5 c: |2 a/ m8 I3 i& e# Kreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .3 e. p. Q& G5 A4 q; A' g8 |
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 d9 v; L2 p+ H" {) K7 oclinicaltrials.
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