LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
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J. Mazieres, S. Peters
/ J1 I4 t O! I5 w& }4 _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
: [: k( u0 ]# [/ R# q0 ooutcomes 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$ F% ~% i( d+ j" X* r- \
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her24 I9 T) ]1 F4 t' I+ B: R
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations2 s& G. |" g! t. J6 {) s
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
2 P( r) C$ O6 v9 |disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
( @, B/ C0 W+ o& Etrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
5 N2 e( @ f, j" v5 m% Ilapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and! m1 s+ l* X a v* {) C9 F
22.9 months for respectively early stage and stag e IV patients. m8 ~- e$ d- O
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
. a" m/ J; L9 ^9 ~3 a' M/ |reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .7 y/ s; ]* `" ^! }. m; L) L3 ?
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
- y/ G/ L1 m8 O8 h: Uclinicaltrials.
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