LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND3 R# j5 D% m( n& |0 p5 Q
THERAPE UTIC PERSPECTIVES3 m7 \8 A2 g' j/ j
J. Mazieres, S. Peters! U# p0 c' u2 O/ T
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
6 s3 d. Z2 V4 p, Q6 Coutcomes 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 targeted4 s. G- q* |& x4 @! d3 ]
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2( U. F+ F! N2 @* d7 x# f) H
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations6 u1 a" Q8 l7 y& ?5 O
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
S0 }% |/ Z1 Y! c6 Mdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
2 W7 Q( s. g( t: O! ztrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
( {& b) g3 L7 ]lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and' H1 d1 t1 B4 ?$ l+ Q6 ?. h' L) J
22.9 months for respectively early stage and stag e IV patients.7 x. o7 d ~ L1 d5 m, l. X/ p
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
. g9 j$ o( `) k; w+ A% Areinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
, \0 s0 U, O* | lHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative- n# w) H) R- L" o& f8 U7 M( s: o
clinicaltrials.
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