LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND' M2 `: d7 \! w1 w8 t
THERAPE UTIC PERSPECTIVES
. K' P* Z3 @! U& B/ l4 pJ. Mazieres, S. Peters2 J2 U+ e) {$ y
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
+ o, z6 I( p# ]* g) `/ R0 I0 uoutcomes 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. M; {+ U3 [2 H
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her27 ~8 Z( c+ X* b' Z
treatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations
5 `/ _% J- D' E4 Mand 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;
: B7 F1 z7 c9 C% S; t, k: l' Vdisease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
3 H6 P" f1 e" J# wtrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to2 k& X5 i. D8 b3 c b' _+ F" P
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
* o m$ O) p8 I22.9 months for respectively early stage and stag e IV patients.4 E9 I1 m5 a% v
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
3 E. I8 }& @- sreinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
5 G/ y( j$ g H9 K! \HER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative+ b# i Y3 h% Q+ w: f1 \$ O
clinicaltrials.
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