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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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