LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND( u: p5 u6 F* i
THERAPE UTIC PERSPECTIVES
( b, h _+ f4 M/ @" t. D" m- G2 pJ. Mazieres, S. Peters9 j# H+ w& h- D3 ^* ^9 W2 R5 ?" 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
7 v W: b) r' j1 joutcomes 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 g0 c5 |" m8 vtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
( h# i& n0 i, A# s' m7 E0 Z$ L4 ntreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations" N# [8 E: b6 D/ o- E
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
2 k2 E5 p4 b8 k' cdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
* F( r+ R3 `& X9 ?# P3 t9 dtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to; n1 F4 Q8 r% h( v0 u9 n3 U" u' E
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
1 }& v; D |) L0 G22.9 months for respectively early stage and stag e IV patients.
+ y2 l" Z) m9 A. TConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
7 M+ {% R3 e6 E- ]reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
+ r, w" S: @1 V, H' `3 j+ uHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative! V4 t# O" c8 B7 ]7 s6 @
clinicaltrials. U5 ^6 C" _7 o
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