LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND8 g) s. q6 W7 O* }1 p; X% |- t
THERAPE UTIC PERSPECTIVES
( c5 W1 U: M* k0 uJ. Mazieres, S. Peters2 B8 K% b& K8 P! f% 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
& p2 F1 w9 D; w7 Foutcomes 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
7 x9 P P) G6 b( c+ utreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2& J' V, p; T2 P7 m5 D
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations+ }2 j9 Q, a1 K4 M1 ~2 E
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
' c6 R- }& `; z( `9 \! u/ Ndisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
4 G! o; V. g9 Z, n" Ntrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
/ d+ @ \) O% I s* n& y6 mlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and! L2 k5 d$ q/ m. V" ^4 ] i
22.9 months for respectively early stage and stag e IV patients." @* k2 H5 _8 E
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,& I J5 N4 ~; G* Q1 S, G4 \$ Q
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
A0 y( w0 q# ^. e; y0 \3 NHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
9 W1 t9 e5 u9 s4 Q* Xclinicaltrials.
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