LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND' A* z+ j6 }7 u& H3 [9 [
THERAPE UTIC PERSPECTIVES' F# s( T a' Q# W4 }* B
J. Mazieres, S. Peters
5 M0 Z+ }/ Q2 Y' c. pIntroduction: 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
4 F* ^+ ?: w4 H0 g# N' goutcomes 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
# V$ a* M A' u: ^; x7 g% [treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her28 c1 m4 E% v" O( K/ |' c& z. [9 n
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
6 P: A4 X6 j) U7 ]2 c9 a: v; {and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
6 n) Z3 B1 T8 Z, y7 rdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for% E6 y: |% B7 c0 u" _
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to7 ?3 }& V" s; n+ Y+ N' S
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
( Q c1 \' l: ^! C/ ^, R! u* e22.9 months for respectively early stage and stag e IV patients.+ a+ _: I, q' r z: g
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC, x7 [. t- A: e/ ~, ~1 V
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .% o8 \% U$ N- P& H' v. D5 D$ q
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative% r% x. o9 O9 R. a1 P
clinicaltrials.
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