LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
5 z, L7 L) q2 _; rTHERAPE UTIC PERSPECTIVES
( J% \# F" E7 H) gJ. Mazieres, S. Peters I4 F" s! ]8 J% [' u1 a
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( U* L7 T3 i3 D+ o, ]
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
y7 Y( t% G0 F% Ntreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
* U0 v5 H7 @8 u1 w* F- etreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
G5 ]: ]! e4 n- D- B0 h7 F( _0 I; mand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
0 g7 X# b8 `' Hdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for3 t6 F9 h* K9 z5 r0 U/ @8 o- _
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to- k4 }* w7 E- c. U* m, z5 N
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and! r7 D! I; o. O
22.9 months for respectively early stage and stag e IV patients.
\ G( u6 R8 T$ l: N+ vConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,! q+ J( e( B1 \! X; F: j
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
- e; {! R( _8 x, u' b. @) {HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 O% l9 P9 i; jclinicaltrials.
2 F! O. l7 s1 j; O; } |