LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND/ D" E: ~! v6 W8 H( u; h
THERAPE UTIC PERSPECTIVES
# n* o/ f% M5 V( yJ. Mazieres, S. Peters
. k% z1 d8 ^- m |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- `3 \( K: _5 o 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
2 G' @' ?7 r: ?* btreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
0 z3 Y6 c4 x8 n" n/ z( G btreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations/ ^8 t4 k4 Q' [3 Y P$ f- E1 ] }! v. M
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;7 A1 n" ~) q8 ^/ o, A
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for, L2 H! v5 u6 ~3 G+ i3 Y% k/ Q" [1 v
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to1 ~4 W. s( h7 u3 S# o
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
. _3 F7 O& F2 w& B22.9 months for respectively early stage and stag e IV patients.
( Z; W* @3 ~" N$ Y" H9 Q' I. ~Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC," U/ y: b& h; X' t# F
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
# j, s0 d/ q8 \# o1 QHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
$ L( Q. w" [* j- Z. N+ T& I( R0 Nclinicaltrials. K6 P J: o9 z1 h* t/ W
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