LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND: L% F* w; @) w! @" ?5 s. J: Q
THERAPE UTIC PERSPECTIVES0 u5 ]2 x1 G- F
J. Mazieres, S. Peters) I& f2 y: A) Y8 g
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
$ L! r+ o6 p0 x6 J/ ^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
+ q$ z" w+ U' t4 V9 h2 }treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2$ l8 j: z: `* z/ V; F1 j
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
1 S w I! u% N$ I/ Kand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;& E. r& V$ ~/ p( W# U5 b) h
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
& x9 W8 O9 W2 m3 b, X$ o0 I r( W" Ltrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
2 u. o Q5 T* R) d7 H" S0 P3 \lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and3 p. x6 B" q6 H
22.9 months for respectively early stage and stag e IV patients.* u' E7 T, [4 k" R. z- L
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
, t$ R7 r9 O0 {6 g- c1 Q) Qreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
- }' y, ?4 v# Q8 RHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
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