LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND- m1 S0 }4 {# R! o- O9 ]
THERAPE UTIC PERSPECTIVES
$ _7 ?8 o- Q U" H! T$ r2 kJ. Mazieres, S. Peters! d1 M5 t3 L6 m6 d0 P: Z5 q
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! F) t! H5 e) g/ q7 k' m& U* |
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/ y6 ]! Y: v7 A& S" E! P
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2/ a* N0 M$ I3 \$ }3 `% x& w5 l* J: f
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
+ X4 @, s3 b3 ~1 T' V* uand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;' I; n; u$ u+ T% e1 y- O" C
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for! G2 ]1 K4 ~7 F
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to/ B% d% u/ H: R
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
: r" V% E3 G, ~6 E O6 j9 p2 z; \22.9 months for respectively early stage and stag e IV patients.
6 ?$ s- C- {+ AConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC," w/ ]8 e; |9 d) ?# ~
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
% O+ d7 L8 z% |HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative& R# s6 d3 M9 |1 J( `7 Y
clinicaltrials.# { j! f; {+ P- J" L8 X1 `
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