LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 r( V# ^# \- R+ r) S% x# o
THERAPE UTIC PERSPECTIVES
9 u' C. ^, r8 U4 i1 h5 G1 V4 X8 S" wJ. Mazieres, S. Peters' s5 E& S( t$ x5 c# b
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
# d V+ S# _5 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 targeted5 U0 P; A5 Y% s8 w8 A. f4 I
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2& b5 @$ e- ]* k" o( W) F
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
* d& u- L" n4 N( J% {3 m; G# iand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
7 F3 P+ v! G6 j' a$ G( K9 G Kdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
4 P. f) S, C/ G! T' e1 e% T) ltrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
. C; p$ D7 [- z- ?) g+ Rlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
- E9 j) c; E/ w1 U4 D5 F B x22.9 months for respectively early stage and stag e IV patients.) T( Y2 [" r5 P
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
c3 D1 e& d/ u% b. {- f* Mreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
- U J# Y1 @& j& h9 ZHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
# C. w, \2 `/ q# j5 B" ~clinicaltrials.
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