LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND. a' \$ S# q- L; l- k# F
THERAPE UTIC PERSPECTIVES
/ d! w$ M) S4 x, F5 t6 n. @J. Mazieres, S. Peters
: j# T8 y( a+ n6 L( Y5 ?. ]* q4 qIntroduction: 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
6 b& S5 a- c( |9 B$ ]" qoutcomes 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
* H& G# F v! a$ } \ v( ctreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
: i( j2 |, O) [# H+ J1 y) o; ntreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations: N& _2 u, K. @ S; @: U" j$ Z
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;- N: M1 e q5 z- V# v* O1 c
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for& t/ ^6 N3 k6 D+ Y+ a
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to- e+ T1 k& k: C1 ]' i# b* p* U
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and7 u4 [* a" D% F6 T
22.9 months for respectively early stage and stag e IV patients.- A. y+ K; ^0 E3 B# K& V
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
8 x# R! ]/ \3 O$ t( @' areinforces the importance of an HER2 screening strategy in lung adenoc arcinomas . ~* o5 d8 x6 \# D; |/ ~
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative- O# m1 W' a: |9 b/ w _
clinicaltrials.
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