LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND7 V0 Q0 d1 O$ l. h2 H" x
THERAPE UTIC PERSPECTIVES
. p) k6 s; q/ V$ @. ~' [ p" FJ. Mazieres, S. Peters/ k; C. J1 u. h. d# {
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
: C4 R) y0 j. v3 v6 O6 toutcomes 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' x& p/ p+ K( O
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
- Z' x* X1 j( ptreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
/ R; Z' g5 b( a& |( Y0 jand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: r& L$ R- @& t/ c0 {, rdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
4 N0 \5 q9 r, l& a! o( `8 Y% Ftrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
3 Y {6 g4 V7 c' J; R9 { s0 Z6 Ylapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and5 w* _& i" M; ]- {7 P. {" h
22.9 months for respectively early stage and stag e IV patients./ S6 `' u9 x" k, _7 J( t
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 ?6 s* n) k8 V# t9 p& ?6 Preinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
; H# z$ g6 v5 v `; oHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative; o/ c3 J! W8 t e8 k
clinicaltrials.) y4 x$ _2 h- s" ?7 h$ g& r
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