LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND5 p' \7 L9 a0 y0 B' G. U- s
THERAPE UTIC PERSPECTIVES
* j5 j8 Z: }2 F) RJ. Mazieres, S. Peters
6 N- _: v. r" f5 D' Y3 e/ QIntroduction: 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
2 C' q# O( ~/ c$ f8 routcomes 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
! P6 h6 I# | j- ~treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her22 z: I! E6 R! e
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
- i- P" T1 c' Y: d& p2 E+ uand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;, W" p) \3 B5 \: M
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for* x& k% a% a2 W6 M
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
& v! Y$ E# ]- ]9 t- rlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and2 j) [& _, s9 b. U/ i* r0 \
22.9 months for respectively early stage and stag e IV patients.4 w# X, c' T y. y) f6 A0 o! X
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
4 Z3 Y& A' f1 r* M, {reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .. N# @: k( R" L+ O
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative' q( ?/ f9 D! V
clinicaltrials.
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