LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND* ?: k; s: N) i1 Z( J
THERAPE UTIC PERSPECTIVES
% o! l8 u$ ]8 C/ GJ. Mazieres, S. Peters$ ?. t: Q) S8 m) I) w. 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 j0 I4 Q: |" O/ f1 y4 G9 d9 [3 Moutcomes 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
1 m j1 d0 o4 |& E. P/ atreatment was delivered after convention al chemothe rapy. A total of 20 anti-Her22 y1 k- n, x J
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations6 p s$ f+ \) j7 ]# s }) ?% C
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;0 O+ F1 F$ U# P
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
- R. a2 B3 A: ]) D9 L0 ktrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to9 {) q6 }5 L, Q! B
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and( }+ x4 O1 n2 E- A6 u
22.9 months for respectively early stage and stag e IV patients.
; Y# e( p3 P# w: s" \Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,5 f+ v5 o. L- X0 |+ f" j9 w/ `; V" s
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .6 x9 U5 T1 n/ l) [' E& Z
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
3 {; }% G; B9 o) y& Y( }( ?% Dclinicaltrials.
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