LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND7 a+ B7 i, h6 |& ~! J6 Z! C
THERAPE UTIC PERSPECTIVES
) l% ^) l+ A6 \5 l' i5 fJ. Mazieres, S. Peters
2 h* L$ o' ^# q1 c9 O0 _2 @+ s. k) 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
# F3 y. N# a. }- R4 _4 z7 n( Xoutcomes 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 G X% z6 H+ @3 ^3 H* H9 i1 etreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2* T9 T* U6 j: q8 t4 v% F0 S4 y; Q
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations' w, x* C. |, K5 [% M) f3 R" L/ f
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
K9 [& C5 r: M4 y9 Ldisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
; u O9 M% @2 w' _& M8 b5 Ltrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to$ e8 N# D! m$ B( m
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
3 a- K+ g# u3 T9 n/ r, _22.9 months for respectively early stage and stag e IV patients.
; ^. z: {- r9 S& M& ~Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,+ u1 [3 D( n6 E0 L
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .- d/ C+ m) m5 k0 C' j3 y
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative! B9 V( t* u: |/ `7 M5 i3 R
clinicaltrials.
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