LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
. `& G0 _' Y6 @% p9 |THERAPE UTIC PERSPECTIVES8 { j# \3 Q/ _) s( A; x
J. Mazieres, S. Peters
9 X* |+ N! ]* V$ DIntroduction: 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" V0 m# {! B2 L" K* k
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' V9 b3 H' s) u: g4 P
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2$ W( ?( T- }4 X' R. c9 x
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations) m' `' z3 i( G1 w _, d' ?
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;9 {7 C, o1 R* N t& @; D
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
9 h6 z% B4 P3 ]trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
* X8 v( A) V0 j; K) U' o1 clapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and4 c( p: }8 h$ Y! z/ g* S1 f
22.9 months for respectively early stage and stag e IV patients., P4 q8 I+ |7 v) w* f( h
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
5 f+ x* `$ @, R/ vreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .( e# d4 x' W8 J. q. P7 {
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative( l: F( `$ K; Y8 p" h
clinicaltrials.
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