LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
$ h( q$ H$ f& _7 k& UTHERAPE UTIC PERSPECTIVES. L8 R6 k) l3 g, g5 j' [
J. Mazieres, S. Peters6 W# a& A2 J* n# {
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
) |4 O4 z% Q/ l3 o5 F1 D) Loutcomes 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
8 L/ \9 {5 S7 z# O; C1 ?9 wtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
; p) G. P: d4 l. t8 M7 I, ~treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
: D' u( m% E$ H5 [' K# p( `, kand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;" t ^4 Q" Z4 z; u8 t( K( A1 n
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
5 |6 a' F5 S6 O8 _+ n ptrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
: S# I$ |6 s8 n, f) Nlapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and4 w6 g) I4 [) e/ F. e f4 d4 Y
22.9 months for respectively early stage and stag e IV patients.( e: `6 V% Q/ ~- Y* k
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,6 {0 A3 u) H0 t, z: A
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
& b5 I) b k+ }HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
4 s1 N" l. N( w( b8 z: zclinicaltrials.: d' S( M7 @/ w- {8 Q
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