LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% N. ^- o8 W" ^1 T
THERAPE UTIC PERSPECTIVES# G' [4 j4 n- N8 s- y N
J. Mazieres, S. Peters
2 I( F ?& U5 A# D# |1 m, 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
5 R1 d) @" U. ~7 ~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
F% p" ~: q: X. g4 |0 B; wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2* i' O0 X- A3 u) T4 r) Y' p- O
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
4 D' `! m$ o! @0 O% q) I7 Wand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;) J7 e5 O. I! j7 I+ \0 p" i$ l; \
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
8 o) T* H# \" I3 I/ h. Rtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
( S% {* `; V6 |1 [lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
8 w% U+ `6 u! @ a/ `22.9 months for respectively early stage and stag e IV patients.
. e9 d7 c# M: zConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,( d4 I! ~! V" W+ Y, F
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
4 Y8 m4 m; C7 i5 o: N4 x5 _HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative/ z1 l! S* N, M4 `1 u' u; r
clinicaltrials.: A* Q. l+ B5 r" s) L5 N
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