LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND" r! z, l! o6 |) S" w0 R
THERAPE UTIC PERSPECTIVES
! [- W) A, s+ T0 V& uJ. Mazieres, S. Peters
* t2 V4 D1 Y0 Q: s% y6 pIntroduction: 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% z2 ?& }: A* f3 u- w: `4 v: A5 s
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" }5 l% j7 A: q8 S5 g
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
2 h5 @$ t) U, K/ Q9 vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
* O% H2 F) J: [+ t" W! ^* land 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
; A( }; W- T" h. A4 K3 U3 mdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
4 Q5 ?) }" T8 c( `! |trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to$ R& J: i) q7 b# W
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
( C- F3 Q T# \/ t2 b& k) c" z P, H22.9 months for respectively early stage and stag e IV patients.( l! o1 ]$ p" w( }' \) ]
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,0 \1 G9 D8 J) x9 T) _2 M& e
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .5 t) I3 {5 ~" H3 K/ x
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative1 P1 m# m2 k1 N: J f4 u* }7 A
clinicaltrials.% l% q$ f) r" @" s- n
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