LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
7 g' t F: J- ]) x- _) TTHERAPE UTIC PERSPECTIVES9 L) R5 r; ] u1 ^
J. Mazieres, S. Peters
9 T1 c8 B1 T1 w8 VIntroduction: 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 v& d" k( [/ ]3 R5 j/ {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 targeted0 u% \. E1 s: _
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her20 t7 {) b2 O) b6 j8 O; a' @
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
' a' B( N- J" _5 {and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;: l% k/ B+ }+ M L8 v, [
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
+ y* |2 d9 h/ M+ h7 Etrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to* ^1 m7 O- p" p4 B0 `1 t! w
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and1 D, h4 @3 Y2 E; L4 o: u+ o. @8 X
22.9 months for respectively early stage and stag e IV patients.: @0 C' b1 J* j& A
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
C7 {( N% \" C2 V, E& jreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .1 R- V5 t/ Z% e6 s9 d9 ?8 t
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative W5 k3 [6 i3 a& G/ Y
clinicaltrials.
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