LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND3 i' C( Y. f4 `! L' S. p0 H
THERAPE UTIC PERSPECTIVES
5 y: [4 d% w, j4 F5 @ BJ. Mazieres, S. Peters- W* H# a# d, X* F; {) N
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
& C6 F- t. M* t. T$ @$ H4 Ooutcomes 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
* ~7 \/ [1 g) Atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2# @6 O; z: z: B. f
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
2 Q# v+ X$ Z. _/ o* Wand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;8 ?4 D5 z; S& O ?
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for/ `( [- w0 d8 |3 N, D+ F- @) D
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
! R2 I& _, G! [) t& v$ @9 e0 S) o9 C; Rlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and# t* y, ~/ W/ l3 S3 J/ \
22.9 months for respectively early stage and stag e IV patients.
* B: U, k# i! f- ~Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,. z* O, v$ G9 B# @& O0 B1 @7 _
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
& w' Q x: H- [% zHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative' C. b# T/ y8 ?/ `! _& q
clinicaltrials.9 N: l) G" L6 {3 t, ]3 k. W
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