LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
9 a0 A& I5 B4 I t) ITHERAPE UTIC PERSPECTIVES
2 Z2 F$ p/ L/ ^4 I- PJ. Mazieres, S. Peters
$ ~# s% X* C1 K6 M2 g- c; X! v4 wIntroduction: 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
( u5 j7 M/ [4 O* E; u. b) o) foutcomes 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
) s/ R, W6 V" [2 Ytreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
/ E# p9 P3 V6 P! z6 |) Ftreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations* v- c* ^* X7 E. h* [+ @% ^4 a
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;6 `$ t. H1 s) D# w6 n6 a3 B t) `
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for# e2 a+ W7 i6 U) \& V' {" ~/ N
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to5 E" i1 i7 Q' g
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
- C: O- k5 X( _( h22.9 months for respectively early stage and stag e IV patients.6 p4 p$ h2 D7 f1 F% A; W
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,9 V) y, b, @( {* ]- x( W
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
& S9 D* {* d6 @1 s9 h6 d2 K( jHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative0 M5 C0 A8 p# U, [7 h
clinicaltrials.
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