LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
6 K- b: I4 j4 W/ c) X, B5 }THERAPE UTIC PERSPECTIVES
+ q! l6 X5 ]! o7 A5 s3 vJ. Mazieres, S. Peters+ u2 o& O! h y1 @+ w$ X9 m& A0 F
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% L& i6 Y1 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 targeted
0 c: o, h `1 D5 _. _# M& _treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her22 S" s( g& O4 I% Z8 i
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations9 L. K2 A7 D7 T& X1 h. g
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
8 o1 l5 q8 Q: o5 p* r1 ^9 _disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
- c8 W1 {5 h/ p6 X' m3 i; W% t0 O @trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
! s/ w3 ~9 l. V# ^& w% Alapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and- D4 z- O9 S" n c
22.9 months for respectively early stage and stag e IV patients.9 j5 K- X0 M7 U: ~/ i2 G+ }
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
. W( s& y" e0 ^# R4 }( c+ e- W' G" hreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .6 R- m4 U: t- A. \; A
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
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