LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND+ R, i% V9 Q, g( ^
THERAPE UTIC PERSPECTIVES1 h5 ]( w5 V/ p" k- x
J. Mazieres, S. Peters
' r7 K) O- a# s( h% N- hIntroduction: 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
7 f4 b2 E: A* j/ 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% e" E* r" c* l& H8 M; X
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
6 J+ B0 `; A# Q. Vtreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
* R0 a4 G' `2 H& Iand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;* m9 c9 M( } k3 t' a
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
; j% {+ s4 o( _- B2 w* xtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
4 Q8 o6 b( u1 F; l, Y2 Flapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and; K, k: o. y& i0 N( ^/ m% y3 P
22.9 months for respectively early stage and stag e IV patients.9 b3 d) Q. N9 K# P; v
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,: ~" u/ g8 y% _' G
reinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .# K/ ]" C; N" W% I3 b
HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative
+ M2 V- G6 j! ?" Dclinicaltrials.
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