LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND `- l5 V& W+ j4 J) b: \7 w: Y
THERAPE UTIC PERSPECTIVES
" T- H- H+ d5 d2 P. aJ. Mazieres, S. Peters, Z/ k/ u) s. Y# n
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
- m/ I: K0 m; Woutcomes 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
, z* ~$ |6 V. J1 b' I; Dtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2$ E: z( F: {% b
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
, m, S0 ]: n3 x2 L7 |# [* G2 Cand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
; y1 u _1 \4 {+ \, ddisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
$ x9 E; w4 ]# T2 Dtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to, q- W& a: B/ `) ~2 E0 i
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and9 Y* Z) I* h r0 j0 d+ V
22.9 months for respectively early stage and stag e IV patients.
! J3 j% g, C- W( `* \# |Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,/ {1 |: p2 M) j0 _7 j
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ." t/ g8 |5 U! W
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
$ C% f/ z( N, ]& @8 Yclinicaltrials.
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