LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND7 ]4 `: h% _, j0 D$ e% p
THERAPE UTIC PERSPECTIVES5 G& {" T, J5 _ h. o% w
J. Mazieres, S. Peters+ Q3 f+ d! J9 K! D8 M5 k+ 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 therapeutic
0 v1 r6 f- |' t6 T6 I) aoutcomes 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
6 C* d; _# p/ A3 dtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
! p0 Q! d7 g& `% n; Ptreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
G/ M6 _ Z& o1 \. kand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;. I5 ~: I* [" g/ K" P: I
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for% H; |! j5 L6 l. |: R5 r1 C d
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
8 ~( Y3 g( z1 Z* f [; flapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
' c: D1 }0 f* a: X22.9 months for respectively early stage and stag e IV patients.- `! S! a" K# ~' C1 H
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,1 m- O$ v: d. W
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
4 z' Q3 R q( \! XHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
x2 O8 I- i+ Iclinicaltrials.# N9 w0 N1 f' `7 b4 G# {( R4 |6 S
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