LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND& S9 k5 L$ ^% G
THERAPE UTIC PERSPECTIVES
; m1 K" s' c. y9 xJ. Mazieres, S. Peters5 i! z: ]- O; j9 J" C/ w
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
! P$ o7 e* f: |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 targeted2 n2 ^" [% c0 P, f& C$ W& w) K
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
; p5 [4 ?8 @: @* R1 ptreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
* \" V. T& D( a. Y8 K( Qand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;5 O0 i) `' l) Q6 v
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
: E& m9 ?3 t! F) r/ E- ttrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to ~. d( L8 N% p% m& z5 }* l1 Q* C' W8 ^
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
# Q. M0 s. ^0 G* o" {22.9 months for respectively early stage and stag e IV patients.
7 f( w5 S6 R6 q$ |$ {/ D+ z8 VConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,% c+ d/ C. ~5 m/ C
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
. U" N$ W- J( b. Z) O' B8 |HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative5 F d; ~0 q1 j/ r: X
clinicaltrials.1 J. t' ]1 R; K _! x& q/ C3 {
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