LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
: |( r! C/ E0 ]4 @THERAPE UTIC PERSPECTIVES
: q- w9 }) K* j& _J. Mazieres, S. Peters
' S0 {3 Y4 \; K: e* x6 h$ x9 ^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
& T/ E$ J, }' X o2 t% N! o- Qoutcomes 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( F% b/ Q3 M8 I& @6 T1 G) V8 M
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her24 n, _ I; L( A
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations/ A- \# {- g' Q: C# `4 {9 j: O7 ^
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ; c& v" N* Q, _$ p& Y1 R* W: a. z
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
% @) h, p# h- O. A% ]) [trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to- J7 Z0 R7 b0 M7 X. I
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and* S( w( f5 z+ A N* h" T
22.9 months for respectively early stage and stag e IV patients.
' l# I6 x C& W7 _Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: C* v5 q/ O9 Z' r5 A8 g1 ^
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .& @( c2 K, I: m* Q# T
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative- |9 g/ r, c6 z: b
clinicaltrials.
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