LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
/ P6 y/ I' l+ Y" q( ITHERAPE UTIC PERSPECTIVES$ {+ ?* P4 k" y
J. Mazieres, S. Peters
A! r% d8 v" V5 `6 N& a3 WIntroduction: 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
% B* g3 l- q" R* joutcomes 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* {+ X/ q* p7 `5 Y$ g9 a
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
. ?- J+ Q" K% N0 y5 I4 H& P. _treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations8 c5 ^+ q, w6 o' k2 C
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ; I6 c, F. _3 B( ?
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for: @' m1 }( i2 T6 g1 i6 F! m1 n4 c
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
' k# |( o6 S9 y: W& p: mlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and9 j6 D8 U5 f: Q$ A, ^$ y4 Y
22.9 months for respectively early stage and stag e IV patients.; o6 v+ [ P/ A9 {, }5 {+ A
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
h" m P6 V e2 ^- sreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .( m+ b v" z F/ K% }
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative/ F+ ~1 u6 M) i
clinicaltrials.$ ]! O" j2 k9 T" _9 e
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