LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND8 m, D/ \( u9 a' S' W
THERAPE UTIC PERSPECTIVES$ m" d' t3 z) X% Y/ a
J. Mazieres, S. Peters
; D6 m8 y5 ?/ dIntroduction: 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! v. n; p( p1 ]( o
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! A, w \" M+ _3 n. E' A
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2" p0 A7 P4 n' J
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
+ I6 Z M6 C) Kand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: B' ?! ~9 {4 ?! n+ u5 ^% mdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
1 D" | {1 F* [: A, E0 {7 Strastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to( V$ C2 a! ^9 c2 I1 ^4 L
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and: P7 X, W6 H( E
22.9 months for respectively early stage and stag e IV patients.* k6 r, [+ A' Q$ _
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,, `# T- h2 f" Q2 w
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
8 O% g& I# Z0 d! V- r3 BHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
% x0 [. B( m$ Y) Z8 ]clinicaltrials.
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