LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND& J) V' {! Z% I3 W$ a
THERAPE UTIC PERSPECTIVES% Z) e5 d6 r6 p8 A
J. Mazieres, S. Peters$ f' a, k7 U) |
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
$ ?( A& p. `. }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 targeted
* L; b" ~+ c5 z& H$ F8 Dtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
) g! h( C) _$ X; n* B* \7 Htreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
6 D3 q% ]5 t9 J- l4 [and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;2 h, S7 t. o% P. L* [
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for( t/ ^* a& M3 L
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
7 Y: w( T& E' |) j) tlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
8 `) k, {7 d7 f5 q/ Q: n22.9 months for respectively early stage and stag e IV patients.
; Z7 c3 ~, f$ }Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
. j# P% f' B7 f7 W1 j+ vreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 D% v- A3 ?" {* G) F' m- x
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative# B3 N0 c* j4 K5 I/ g1 b, A) ]- V$ j
clinicaltrials.6 q/ S! Y; G$ p- R
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