LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 r+ M: f* x- b2 M! p
THERAPE UTIC PERSPECTIVES% ^# x3 y8 [) M- v+ _2 ]1 X" H
J. Mazieres, S. Peters- Y4 M/ W9 |, i
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
7 e4 p4 ~/ J0 \$ V. u* z* }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" V& H& m6 k: G
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
5 H/ ~! F5 c& N6 h& h! Jtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations7 G* D7 Y3 F5 T, w4 E0 O
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
+ N; I$ W$ J- g6 F# Y# i! adisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for' h1 y) O) f: O9 m9 y, x4 T- M
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
1 G# g2 D$ v- ulapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
6 J( R9 U$ T" }6 ~/ J22.9 months for respectively early stage and stag e IV patients.
) I: f; _( u8 PConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,+ Z, L+ M0 X* N5 m/ W
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
, u& G( f* Q ^! g9 e' A& bHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative5 C4 w2 X8 B |' o% J
clinicaltrials.
f0 L! _. P$ T$ h& x+ u |