LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND3 b2 v1 _. S1 V* O
THERAPE UTIC PERSPECTIVES5 g8 L! ~2 V0 d0 l: Q+ T
J. Mazieres, S. Peters' H* q. F6 h9 ]8 N: U/ p
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
3 I# |0 o# T" l- r: E, G) z# poutcomes 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
# O' q L7 Z+ n: ] Y f5 e+ r* atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
- A4 a6 x' B) I4 d/ Y9 Ntreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations& I( f5 Y; z4 O1 [) _# o% L
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
5 w- f/ ^. ]) |6 q* P# [5 Tdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
* K3 ~- i5 y( M8 dtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to% V9 v' s0 d& v6 Y# A! F3 p# E* @) ?
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
R( W( B& B, Y7 d; d22.9 months for respectively early stage and stag e IV patients.
# h) c" [0 Y! o& Y0 {1 P5 jConclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
5 h. @& \$ q. D) B. W- `reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
g9 C G* l- a8 O: W" U/ _1 XHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative# a; z0 s' H" a/ A, d
clinicaltrials.
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