LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
. w+ c9 o3 Z7 e Y4 z GTHERAPE UTIC PERSPECTIVES
a. v, U7 a" iJ. Mazieres, S. Peters) T3 W1 I, @: \, W2 n# V7 T4 l
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
! j' d2 @1 f8 @5 Woutcomes 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! W1 `5 P, q8 G1 a6 ]
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2- i! F5 s1 l' v# X
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations% ~6 b9 \# U0 h; J6 R
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;$ e! s9 h+ F! T8 Z
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
6 ~$ d5 H1 @% f7 W: ptrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to* S' d8 J u' i9 ^5 x
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and* n+ @( \0 h% @
22.9 months for respectively early stage and stag e IV patients./ ~1 E" y5 Y: o+ W
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,2 ~! t) B( K) n. U. A6 ?2 t1 m
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. J8 w9 x A- DHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative- y# T5 N7 b! x
clinicaltrials.
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