LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND% o% r6 w' b" @" p
THERAPE UTIC PERSPECTIVES
- n, n. [7 q* z' i: hJ. Mazieres, S. Peters
9 J d X( l. \. O3 |, C( r# l: k' vIntroduction: 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 therapeutic2 @, r3 s8 ^. V; M# F3 B
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/ G. E6 g/ h! I) R' h h- i m# m7 d
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
+ y/ N; r) r5 L0 ?! E) Dtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations5 I' U. M7 G1 A$ S) x1 M" h& m
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
7 {7 D. B1 w: k/ B& e' Wdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
3 z) m- p; d& |" _+ ~* H6 Dtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
* a" J0 R* m/ L% Y {lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
, ?) p8 [) [' R8 ^$ T; T22.9 months for respectively early stage and stag e IV patients.
3 d, O7 z+ A9 f$ n1 |Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
7 ?% H+ {! S0 D- ~3 Z! _reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .# p; r9 H6 Q. C5 A* I; j3 l
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
8 T/ e$ d9 x8 H" F. Mclinicaltrials.
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