LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
: ~+ k: `' \, B# J# q. X; LTHERAPE UTIC PERSPECTIVES
( P0 h. A# o% vJ. Mazieres, S. Peters
# K5 z# P. `) d+ T' G v8 Q4 |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 w% t' E; x% z# {
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
* D5 B+ M) U, L' }6 Atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
# T, E/ A5 [$ l/ [9 vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations. R" {8 h! q9 o
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
[9 E+ J j+ z" ddisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for; F. L( e+ P# z# ~0 ^2 `1 \! Y, Q4 t
trastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to/ v7 X' m5 j0 ^7 k/ q
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
2 H9 Y0 r3 R$ b7 e6 b& [22.9 months for respectively early stage and stag e IV patients.& y/ M2 V. e8 E6 Q
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
" o& E u* X9 O9 |* _reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
- p5 n% j: G4 |) E% n6 vHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative/ X3 h* m9 g" F, c, H' ?
clinicaltrials.
( }# f$ S$ s( u: v( { | |