LUNG CANCER HARB ORING HER2 MUTATION :EPIDE MIOLOGI CAL CHARACTE RISTICS AND
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J. Mazieres, S. Peters
* j8 h( o- j" B7 l7 [; MIntroduction: 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 therapeutic2 X' V+ e' p. W' P9 C, s
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 targeted4 G. ]/ o2 F K4 e" _( q1 O
treatment was delivered after convention al chemothe rapy. A total of 20 anti-Her2
- s! l4 {7 c& M- r, Q! u4 Ptreatments were eval uable. We observed 4 progressive dise ases, 7 disease stabilizations. h8 y* G8 P7 w2 h) X; n2 m
and 9 partial resp onses according to RECIST 1.1 (overall response rate ORR = 45% ;( C8 u$ ~& l# b: e' c1 u# d
disease control rate DCR = 80%). Specifica lly, we obse rved a DCR of 92% for
3 V! {& p B0 o* v! z& L+ {/ M9 otrastuzum ab-based therapie s (n = 14), 100 % for afatinib (n = 3) but no response to
: J' d* o2 B% N6 |3 Y. D8 glapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and1 Y7 p9 W* u0 t$ K. G# w* u
22.9 months for respectively early stage and stag e IV patients.3 ~0 ~' `! h4 _& k6 s) z/ r; c
Conclusion: This study, the largest to date dedic ated to HER2 mutated NSCLC,
6 q; Z& s/ K- L0 Areinforces the importance of an HER2 screening strategy in lung adenoc arcinomas .
/ [! x" H! `/ nHER2-target ed drugs shou ld be tested further, ide ally withi n large collaborative( z- N6 n6 g; I* \3 F/ U
clinicaltrials.
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