LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND# ~0 q7 f Y, ~- ?# J/ _
THERAPE UTIC PERSPECTIVES- g _2 J" s5 k) q
J. Mazieres, S. Peters* q$ R2 e& |( h, }, p% i8 ~
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
+ _/ G5 E. y9 u' M, P& [8 woutcomes 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
, Z" Y# Y" m7 z+ f3 v2 itreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
- {2 m4 x- v w. I$ z( ~9 [$ n/ \treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations$ F+ N; c* s* p6 Y0 Z
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
( y5 E' f, n2 |8 V3 O0 r1 ydisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
" f' b# l7 T: N4 A* w1 r+ p" btrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to! h E3 W+ B+ q- [
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and8 d0 G) Y$ B9 E' J j: V& p5 ?
22.9 months for respectively early stage and stag e IV patients.6 j3 C( k$ s2 U2 t5 C6 j* K
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,' E) }. `# M4 M* W+ S: x
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
5 w% `- M6 s8 U/ z) a9 }( OHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative8 N$ \8 Z: a. N* e, |' n6 ]
clinicaltrials.
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