LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND' z1 I `1 p1 \: G9 Y2 k; F9 t
THERAPE UTIC PERSPECTIVES
. g0 ^5 b. ^: ^J. Mazieres, S. Peters
# ]5 i6 Y b7 i5 nIntroduction: 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
2 H/ x, a5 W8 ^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
7 k7 } y, r5 f% s" s8 M4 atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
8 B2 R- |2 C7 h T7 ztreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
8 L+ V" Y3 v0 vand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;6 N, @# Y! u# A5 Y& e6 b* R- Q# n
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for3 e; k/ E5 I p5 \+ T
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
3 v* l% G& \2 O# Alapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and) N6 h7 E9 t) {( d ]4 S$ S9 [
22.9 months for respectively early stage and stag e IV patients.
9 l1 Q1 `! r% f0 m6 o$ UConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,3 f/ i( }5 r [! D$ ]1 a# _& t
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
/ B& j- f G6 d( ^7 aHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative- Z0 y j2 M4 G: t5 p! n
clinicaltrials.( e( ^0 Z) J( W6 A* |4 Y6 P
|