LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND' Y3 o; i! B/ C: D+ X
THERAPE UTIC PERSPECTIVES
+ y' \& {0 ?- u+ l' wJ. Mazieres, S. Peters" S$ M. ?* l$ u5 O
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 therapeutic1 x# N/ W) f5 q* {3 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
) x( J+ L- p0 \9 U7 O) p2 L0 Jtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
3 @( Y5 i5 m$ @! H% E3 ^treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations q/ j% Z& E2 w9 u) Z/ y
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
3 [6 B" q. B E7 ndisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for# ^: ?5 |8 U) P9 C2 K/ f1 b
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to1 D/ \: J/ ~; K- v0 J7 a
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
* X- C A' k- x3 P/ Q22.9 months for respectively early stage and stag e IV patients.
. J7 k/ S. x' f, IConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
5 k: a; _6 g- T0 n i4 Preinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
: `3 P- f$ z; z, Y7 c/ A+ f" {& {HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative; `. A) F- a O
clinicaltrials.* ]& K! U. c- [7 W9 {2 B5 Q
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