BACKGROUND:
Current
evidence suggest that Trabectedin is particularly effective in cells
lacking functional HR repair mechanisms. A prospective phase II trial
was designed to evaluate the activity of Trabectedin in the treatment of
recurrent ovarian cancer patients presenting BRCA mutation and/or
BRCAness phenotype.
PATIENTS AND METHODS:
100
patients with recurrent BRCA mutated ovarian cancer and/or BRCAness
phenotype (> 2 previous responses to platinum) were treated with
Trabectedin 1.3 mg/mq i.v. q 3 weeks. Activity of the drug with respect
to BRCA mutational status and to a series of polymorphisms (SNPs)
involved in DNA gene repair was analyzed.
RESULTS:
94
were evaluable for response; in the whole population 4 complete and 33
partial responses were registered for an overall response rate (ORR) of
39.4. In the platinum resistant (PR) and sensitive (PS) population an
ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and
73.9% respectively, were registered. In the whole series, median PFS was
18 weeks and median OS was 72 weeks; PS patients showed a more
favourable PFS and OS compared to PR patients. BRCA gene mutational
status was available in 69 patients. There was no difference in ORR, PFS
and OS according to BRCA 1-2 status nor any association between SNPs of
genes involved in DNA repair and NER machinery and response to
Trabectedin was reported.
CONCLUSIONS:
Our
data prospectively confirmed that the signature of "repeated platinum
sensitivity" identifies patients highly responsive to Trabectedin. In
this setting, the activity of Trabectedin seems comparable to what could
be obtained using platinum compounds and the drug may represent a
valuable alternative option in patients who present contraindication to
receive platinum.
0 comments :
Post a Comment
Your comments?
Note: Only a member of this blog may post a comment.