LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND6 A& H0 [' y; H/ M% ^7 y
THERAPE UTIC PERSPECTIVES d* F4 n* O: v4 F2 x* t
J. Mazieres, S. Peters
8 w5 V0 \# \* w# K3 eIntroduction: 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 therapeutic3 H ~% l' ?7 h3 r0 p
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
) z' O: H, B1 a; z/ H+ H. wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
- ?& L4 G" [) j5 g& e$ P" Rtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
2 v. d! B& m' J G4 X4 H+ A$ tand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
' c8 a( v/ i% G; M* D, Edisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
/ a1 f: W+ v0 i/ z) B) Strastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
" G8 r/ ]8 u# ]' Z: q! clapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and% g. h$ }' g4 v) G+ [
22.9 months for respectively early stage and stag e IV patients.
5 n# L+ a/ e! }+ G; [# F ~" ?Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,! g G# X5 y# q
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
7 Q/ J" M' D9 I4 X, ^( d" A3 tHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
+ i, w, p& \" n9 X: Y; }! V- |6 q8 hclinicaltrials.
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