LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND! p! E- |1 f k/ j5 t$ R, ?1 ^' ~' M8 j
THERAPE UTIC PERSPECTIVES
* S3 q4 T8 w- r1 a1 uJ. Mazieres, S. Peters
( o' F' q6 ]4 ^% ]4 X' bIntroduction: 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. x5 P( i; {# m! @8 K# q$ O
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
3 Y3 f: Q2 V e* qtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2& p; b: T- h/ r, T) a
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
& w' V# q% {+ [. Fand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
& D. {+ e K. A/ A9 Jdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
' h4 X* A# q* w- x) `0 ztrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to& A( X; R# k; _6 P
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
+ r% d2 h, H7 W6 q3 ^* J5 p22.9 months for respectively early stage and stag e IV patients.% @1 u9 I' P9 a" h0 g
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,6 V* \2 n! R7 }: w' a. p
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
* n* F2 J3 ~% l4 }4 o2 D- IHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 I! N5 ~! F6 L, K8 O2 O2 q" y3 k5 m% qclinicaltrials.& Y* w# L! L" D1 ?
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