LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
7 J2 U! U4 C( N4 e4 aTHERAPE UTIC PERSPECTIVES' u" M: y2 ^3 A. a1 M( \
J. Mazieres, S. Peters( @% l; {6 o8 I4 L4 g) ?
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 therapeutic3 q/ S2 t/ u9 r) z' f- \9 l* b
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* g7 X2 Z0 N) B6 A: C+ m0 j
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2! c9 ^1 N% D) s: }/ }, N% E. Z; s2 T
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
$ L. N9 K6 g Sand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
5 ~4 i _% D3 a# R# i1 Fdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
1 b! e( L# j4 M P/ P* Btrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
) |. z! ~! j" C1 x% P% tlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and* Q" d4 ?- d$ Z9 i" U
22.9 months for respectively early stage and stag e IV patients.
, u0 y" h+ _$ |Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
- O$ T1 C5 G. l, f2 d% ~. Jreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .0 S# ]6 R1 x( {, Y% a4 H
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
. f& f' |! b0 ~1 kclinicaltrials.
2 ~4 c2 V1 B0 d |2 `9 m |