LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
$ Y/ o# Y* R! b: FTHERAPE UTIC PERSPECTIVES
& s9 c, w7 X1 `1 [; E* x' yJ. Mazieres, S. Peters
" x9 l# i8 b9 o( K2 m0 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
' g0 N+ I' R& e! F! w+ t; Loutcomes 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
0 q1 C9 _9 c2 y4 D) Btreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
/ T) N0 z. d% v" F: Qtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
- x' q* a# B6 D# k( Y0 _+ o% o kand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
4 ] d* y; R) ? T |5 ddisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
- a4 v' f! f+ o: etrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to/ n) e3 j" ~- ]1 {
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
+ C2 z4 k+ ^6 |3 {0 o1 d" j22.9 months for respectively early stage and stag e IV patients.
) r2 J3 @/ \" q, p- [Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
0 A# |* R+ E; \0 Wreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .9 L) l# b# A- o9 u+ g7 s
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative! ]0 w5 E) V- B0 B6 I b6 p
clinicaltrials. E. s: r `6 u ~$ O' j6 E
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