LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND9 Z2 Z3 ^3 o& i2 K7 o B
THERAPE UTIC PERSPECTIVES
3 u1 d, e7 E( a" S. e1 I" k- o! fJ. Mazieres, S. Peters
5 w5 [3 N6 [3 I/ [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
5 W' n. s$ X6 O) n* E( {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
: w, Q# ]# u8 a Ttreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her28 P- S* K; { }* y
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations% }; N9 M3 T0 U+ @, Z. H. q
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
7 X3 F8 i8 S3 o8 I! C/ w; fdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for: W% v2 ]& U6 S
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
1 a/ y" d$ \) `/ W3 J: W* Flapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and% E' i- ?* h, B9 m' g( t: ^
22.9 months for respectively early stage and stag e IV patients.$ r3 b9 B3 Q9 o0 h
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,$ b) e" A7 j2 S" |, H9 V% W* g8 O) V
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas ./ w6 P' P R/ q, P
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
( Y V* i5 j" O' A' S. J! I( vclinicaltrials.& ]' |2 N+ K/ i) V, p
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