LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND+ H# y# X9 l6 W6 {; k$ d8 k1 Q" X
THERAPE UTIC PERSPECTIVES
+ Y; B s$ R J, a7 f+ iJ. Mazieres, S. Peters6 O1 _! y( a. M$ W
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 therapeutic8 H2 i. c0 \/ K3 P3 U B9 H
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
' v+ g4 h, J! Gtreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her25 l7 b o" t0 r& b
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations; c% \' J) Y/ O
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;; P: j4 {2 B" x3 x4 u, u1 ?& v
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
S2 ?5 Q( L! W5 @: _9 atrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to$ o: s+ Z/ n9 Z
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
7 y' S, S! ?9 R7 u5 v/ L( G22.9 months for respectively early stage and stag e IV patients.& K- n+ a: e |! g0 Y9 |8 P
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,6 i% R( s9 B9 c. w( w
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
5 k3 Z* ^+ ^ B0 L9 X7 yHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
' J& V% |& E G/ T. b( bclinicaltrials.6 e+ L* {) u! P" _% ?. C0 T: ^
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