LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND3 _: a5 m9 [/ T0 c# S
THERAPE UTIC PERSPECTIVES
) d6 R- w, T! b% i8 l. kJ. Mazieres, S. Peters
# }+ N& V* ^ A. 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 therapeutic1 B0 _, U: j3 L" X
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 targeted8 I1 N5 ?% V: p0 H- `' F2 C
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2. v, u! O6 [# j0 u- l X
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations. i5 y0 C* a. [+ d; l$ d6 u/ f G
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;6 _% c5 U; o: o8 W
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for8 f+ b% ]1 @. r. N/ |
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
9 ]% E. S! F& I5 ?" u) ~lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
' E9 { j' S5 a1 `/ n: p22.9 months for respectively early stage and stag e IV patients.! b; W' ^ k- i
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,2 d$ V- W, \! j& k0 B( p, ]
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .# T$ U6 b v) Z
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 b) ^$ k1 b" P" S. ^) i
clinicaltrials.
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