LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
1 ~% ^9 N K" W- [# D0 G* STHERAPE UTIC PERSPECTIVES# j# r8 `; `* k9 I9 x5 m# U
J. Mazieres, S. Peters( d$ C6 d8 f2 B/ ?9 F( h9 E) s
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
m/ C+ T; P; Y, w2 |7 s z* |# c- o8 Routcomes 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 targeted9 v6 ]4 f! W% m2 g" {$ Q7 o% x
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2! R0 V& E+ U# i5 L, s
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 ^6 e; P E7 W2 N, G
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: {0 @# l# E! x, [% {$ j0 ^% ndisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
4 G. d g) M& {- Itrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
# c, U I" c. c, tlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
0 _* ]$ g% G+ `. ?# D22.9 months for respectively early stage and stag e IV patients.) y/ f6 ~& q" W( A
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
# z) s. D8 [" _6 [) L k! dreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ./ d& ~0 z9 q$ g D% Z+ F% l1 L
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative0 Q+ d; f0 Y4 M7 T$ W N
clinicaltrials.
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