LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
' {* B6 A% |+ m3 W1 pTHERAPE UTIC PERSPECTIVES
# t6 m" }6 c$ k5 WJ. Mazieres, S. Peters
# U, E' M9 |" Z& U: ]3 c- O$ WIntroduction: 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 therapeutic9 o$ s, K' j. X* p4 U1 D* @
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 targeted
- a# ^: u8 Z% I! N( Q; E) q! itreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
4 p7 \. s! W; g" N' k% F# gtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations% j0 ^! o; ~ X- b. d) l
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
+ K/ n: _7 Z O6 X& N2 L& Ydisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for" I' r# r1 s" M# l1 z Y
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
) @, D% Y2 o/ ^1 r4 W2 N. Rlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and$ C/ J! ?5 F+ O5 `6 h/ M& e8 x9 ^7 ~
22.9 months for respectively early stage and stag e IV patients.: ?5 R6 Y: \, o& w& y
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,$ j3 ]+ ]; I+ p1 d( I1 s- [8 x
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .' o& p2 I5 Y. g g
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative' W6 R" z( R% h0 a% G2 E) [0 m
clinicaltrials.4 {" g1 w* n! @, }2 e
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