LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND- A/ y& Z' O) U, D) y
THERAPE UTIC PERSPECTIVES( B A! z/ }* S) `
J. Mazieres, S. Peters
8 S; X; C) R; M/ b4 FIntroduction: 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) O3 ] y4 ^) |/ B' Q
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
& g6 W. y/ K9 u( M1 ?' h& T# w& {# _: qtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2. E: F2 \) S6 _
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
; x! ]4 C: M2 s3 c& [and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;6 f5 ?) P- f. U3 n5 p: u
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for: o& `$ F; k- k
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to# D4 i: \: w# Y& i9 d j; {
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
) X6 u# K8 W' C/ s5 {$ b22.9 months for respectively early stage and stag e IV patients.7 l2 p# U8 t3 t* j& E* n
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,2 r7 V3 p' M" `5 P1 H6 C
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .- T& r% H7 y: s+ A7 L2 K
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative0 G: V7 V @0 q9 b
clinicaltrials.
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