LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND' k6 l9 k8 m6 d4 d8 [+ }2 |% a- ^2 I5 o
THERAPE UTIC PERSPECTIVES
. K, d6 a3 B- v( DJ. Mazieres, S. Peters
4 N& c, m' v! N# {: i: B6 yIntroduction: 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
/ A& L' P' j% J4 m6 i6 noutcomes 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
' w- U5 d9 r1 Q: `treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
% X" d) \/ T6 q3 c* Ctreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations; k* v5 q- k( q+ u+ J8 R8 Y
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
( ~5 a% h1 R& l* mdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
, e1 n( n1 @. {/ c* a9 Rtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to& Z9 {+ y5 ?' Q$ c; E M* k! d
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
" i3 H8 T0 m) o% ]* ~: v22.9 months for respectively early stage and stag e IV patients.! b7 z9 o! i% q) l
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,; _9 F+ X4 m1 E! N% n4 ^* d
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
, M" K4 S2 x& r, THER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
; w( z4 ]1 b# o/ P6 X% nclinicaltrials.
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