LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND- o: K6 C+ S" n8 i( z7 o. W& j
THERAPE UTIC PERSPECTIVES4 C# N. `* l& Y! Y0 i' F3 e
J. Mazieres, S. Peters
) Z& \' Y9 k- B) [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
+ q; e9 A& _4 l2 B# S; ~1 aoutcomes 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
5 h2 }& F: r% @* }; Q. otreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2( O8 B% B0 S7 O! a
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
/ Z- h4 I* u* K- [and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
8 c7 \- F" U* V1 X2 Vdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for* @0 h+ h7 U* f- v% v0 M% l6 a+ n# n$ p
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
9 @% b/ l5 R+ X& {3 W3 L. Ylapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
; U9 ^8 a% j) `. H: J7 ^* T22.9 months for respectively early stage and stag e IV patients.
1 K5 H2 Z) w( c, t$ O8 RConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,+ I3 J1 P( [+ i) {
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
4 A0 k: K. ?7 gHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative/ G O0 u* Q* ]4 X7 D9 H
clinicaltrials.- z$ g: L& [$ n0 d/ P, f9 _3 B8 h, W
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