LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
4 g+ W+ b/ I) r5 T+ k+ X. pTHERAPE UTIC PERSPECTIVES% `0 e$ d$ G. J
J. Mazieres, S. Peters2 V1 k9 W, e+ p1 z
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 therapeutic1 x; `9 b2 A S& P
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 targeted5 U1 n, `! R4 u! u, `9 L( F, {
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
: B$ h1 I. g; [" ytreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations, g! L6 ]' L( _- U& Z, c8 n$ P* q
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
0 e$ P6 T% d9 u5 ]/ w& T% p) j9 \' pdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
9 a$ p8 s. y; I/ Dtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
c' P3 K, _. H/ [# [8 K! R- E! ~lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
" \$ ]" @$ N i4 v8 R22.9 months for respectively early stage and stag e IV patients.% H/ B/ |+ T3 m' x `; k: N2 Y
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
- ?; c7 C' u1 j0 v1 V8 J) r. Freinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
5 ?8 j) a8 ~3 [7 r( H# ?5 [HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
/ D! ^' O1 n4 j9 L. |4 ^clinicaltrials.
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