LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
5 ]' H% I0 q9 z' ~ y, K4 PTHERAPE UTIC PERSPECTIVES
0 c( _, a9 E7 p% C, Q% L3 eJ. Mazieres, S. Peters s7 f4 t+ i7 |4 U- }2 r
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
6 I8 w ]+ H! @4 |. doutcomes 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
" Z1 U! i' F$ C% z! h- _; n* }treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her21 O- J: |8 e: m9 r6 x% _
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
w$ {$ F2 H/ Zand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
( |, Y, Y; @* p( m1 ^ ~3 m& ]5 {disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
: I2 o5 D* {6 P1 u' ~. p$ T) @trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to2 i2 G5 d( R; {7 z5 o8 W- i
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and+ D0 R- @* A) j* `" g
22.9 months for respectively early stage and stag e IV patients.' ]4 a. }2 V' D8 g Y0 `
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,5 F$ E) C4 c8 i& W0 I3 ]% \+ |
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .* l; Y/ _! [. \/ b7 {8 T% L
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
8 @. Y2 s- o+ T# r; e5 |clinicaltrials.
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