LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
8 {9 Y8 \4 d3 A) lTHERAPE UTIC PERSPECTIVES8 d1 o) L& [3 f3 x: e3 a1 ?
J. Mazieres, S. Peters
3 s+ y" ]5 G" ?* Y9 `& QIntroduction: 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
" C- p" U7 K) O; e. |. S( Uoutcomes 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+ m' L4 a1 r, d- C8 |# z
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2/ E6 b' C6 y* m- @, v& J
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
; V8 d: z! A3 f0 iand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
2 @/ O. a! n4 c7 c4 Vdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
/ R- F" @3 K* _. f: H0 O9 q& Wtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to" _& V1 i( c1 Q6 W. V
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
+ g7 ? z c9 l1 t7 J2 `22.9 months for respectively early stage and stag e IV patients.
9 e |4 ~& n; q9 M' k- R q. `Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC," g5 z2 g* Y" P. L
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .2 S' |: j# {, R0 ]$ ^2 L" ]
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
& T! p% t1 @: J& Uclinicaltrials.& g1 K$ ]6 ~: b$ e c
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