LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND! U }! a& y& E2 F( C
THERAPE UTIC PERSPECTIVES" C7 F, v1 s9 n' g$ K
J. Mazieres, S. Peters
/ K, F' k" n6 i8 Y4 _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
" \& o2 c/ p. O toutcomes 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. v% }: C8 d* c- T1 `3 n+ N8 \; f0 Btreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
/ v) g0 f8 _7 X0 |treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations6 ]7 k& E0 Y* k" u
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;) C* d7 L! t. a& q9 I
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
: b5 q$ S2 E( x/ ^1 {7 `2 Otrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to" g5 k) N4 J9 e$ n' r) O8 x! R
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
9 j# s! N8 X6 a" f' Q- s22.9 months for respectively early stage and stag e IV patients.9 N2 e+ W; r5 Y: {
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
. E. u% P2 X' R" t$ vreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .4 e1 \5 S" H h: B
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative% e. q' z8 r9 U$ O
clinicaltrials. u- [" W& Y6 U1 y( B
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