LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND7 \' M+ J7 @1 H( }" S4 |" W
THERAPE UTIC PERSPECTIVES
$ ?9 ~7 e" Z( \; I. E! [J. Mazieres, S. Peters
# b6 h/ j5 [; i4 \; gIntroduction: 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
O) o$ U& e" w1 d6 `" Loutcomes 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
: T9 O8 {# b' xtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
9 T) n2 f1 A+ `- s$ Wtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
2 R8 W: T. ]+ p& cand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;& l8 L+ c+ E2 Z* u- \& w
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
! m* i$ J8 `0 ]' r: O) y3 A3 {trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to, T4 L6 @, l/ Q9 P' Y8 X5 I& |, U
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
7 s) U/ u/ k1 N. e u22.9 months for respectively early stage and stag e IV patients.
* G% F6 U/ r% {$ v5 ? t5 lConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 Q8 V5 C6 K: x; |reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .& ]* {: D6 f6 w( E& s( x G7 d
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative9 K0 n1 N3 A. j- e' t
clinicaltrials.
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