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- Anand, Aseem, et al.
(författare)
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Quantitative imaging by automated bone scan index (BSI) as a response biomarker in standard clinical care of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide
- 2015
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 33:7 Suppl, s. 288-288
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Konferensbidrag (refereegranskat)abstract
- Background: Enzalutamide (ENZ), an androgen receptor antagonist therapy, was approved for patients (pts) with mCRPC. However, in standard of care for mCRPC pts, change in prostate specific antigen (PSA) is not accepted as an efficacy response measurement and the radiological change is inadequately measured in an interpreter-dependent subjective analysis of bone scan. Therefore, an objective efficacy response biomarker is warranted. In this registry study, we evaluated BSI as a quantitative analysis of bone scintigraphy, to access response in mCRPC pts being treated with ENZ.Methods: Pts with mCRPC, at Skåne University Hospital (SUH), Sweden, who initiated treatment with ENZ after failing chemotherapy were eligible for the study. Primary objective was to associate the change in BSI and PSA, after 12 weeks (wks) of treatment with EZN, with overall survival (OS). Automated BSI generated by EXINI boneBSI platform is quantitative representation of tumor burden as a percent of total skeletal mass. Bivariate cox regression analysis was used to evaluate the association of BSI and PSA with OS.Results: Thirty-five pts, who initiated ENZ treatment at (SUH), were eligible for the BSI analysis. Follow-up scans for the BSI analysis were available from 24 pts. Median baseline BSI value was 2.92 (range: 0.0-11.72) and at follow-up the median BSI value was 2.83 (range: 0.0-12.65). OS was associated with BSI at both baseline and at follow-up as opposed to that of PSA (table 1). The change in BSI between baseline and follow-up was also significantly associated with OS, whereas the change in PSA was not.Conclusions: Automated BSI and its relative change were observed to be associated with OS in mCRPC pts receiving ENZ as standard of care treatment. The result deserves further validation, in controlled investigational studies, of BSI as a quantitative imaging biomarker indicative of efficacy response to second-line treatment in mCRPC pts.
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- Bonnefoi, HR, et al.
(författare)
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Phase III trial (EORTC 10994/BIG 00-01) assessing the value of p53 using a functional assay to predict sensitivity to a taxane versus nontaxane primary chemotherapy in breast cancer: Final analysis
- 2010
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 28:18
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- LBA503 Background: Predictive markers of response to chemotherapy are lacking. Preclinical data suggest that p53 mutated tumors are resistant to anthracyclines and sensitive to taxanes. However, clinical data are contradictory. Using a functional yeast assay to detect biologically important mutations, this study tested the hypothesis that docetaxel confers a greater advantage over anthracyclines in p53 mutated tumors (mut) than p53 wild type (wt). Methods: Patients (pts) with locally advanced/inflammatory or large operable tumors were randomized to either a standard anthracycline regimen (arm A) or a taxane-based treatment (arm B). In arm A pts received 6 cycles of FEC 100, or tailored FEC + G-CSF (Swedish cohort). In arm B docetaxel (T) 100mg/m2 was given for 3 cycles, followed by 3 cycles of epirubicin 90mg/m2and T 75mg/m2 q3 weeks (T-ET). After chemotherapy, pts underwent surgery followed by radiotherapy. Endocrine therapy and/or trastuzumab were given according to each center's policy. Fresh frozen tumor biopsies were mandatory before starting chemotherapy: frozen sections were examined centrally and the p53 test was done when the invasive tumor cell content was > 20%. cDNA derived from tumor-extracted RNA was transfected into yeast (Flaman et al. PNAS 1995): tumors were deemed p53 wt when there were < 20% red colonies (background) and p53 mut > 20%. The three co-primary comparisons for the endpoint of progression-free survival (PFS) were between arms A and B in p53 mut, p53 wt, and the entire trial population, each at a p=0.02. The sample size gave sufficient power for an interaction test for outcomes between p53 mut and wt at p<0.05. Results: From April 2001 to November 2006, 1,856 patients were included. A total of 386 pts (21%) were ineligible (including 292 pts with <20% tumor cells and 67 without sample). No unexpected toxicity was observed. At the time of analysis 675 events were registered after a median follow-up time of 57 months. The results are summarized below. Conclusions: p53 is not a predictive factor of response or resistance to taxanes, although it is, as expected, prognostic (<0.001). PFS is not statistically significantly different between FEC and T-ET arms at the 2% cutoff level. [Table: see text] [Table: see text]
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