The role of biologic therapy in phase II breast cancer clinical trials.
e13048 Background: Molecularly-targeted biologics (BioRx) hold the promise of improving outcomes and reducing toxicity of breast cancer therapy. We evaluated outcomes and trial characteristics of recently published breast cancer phase II trials (BCT) compared to other systemic therapy interventions. METHODS: We reviewed all English language phase II BCT published between June 2005 and June 2010 identified in Pubmed. Eligible trials reporting disease specific outcomes were each abstracted by two investigators. We recorded intervention, treatment setting, correlative science, and disease outcomes. Results were analyzed by descriptive statistics, chi-square analysis, student's t-test, and Wilcoxon ranked sums test. RESULTS: 297 trials enrolling 18,319 patients were abstracted. 98 (32.7%) trials incorporated 31 unique BioRx interventions. Among these trials, 37 (37.8%) used BioRx as single agent therapy and 61 (62.2%) used BioRx combined with chemotherapy or hormone therapy. Neoadjuvant BCT were less likely to include BioRx than metastatic trials (17.4% vs. 37.2%, p = 0.006). 1(st) or 2(nd) line metastatic BCT were also less likely to include BioRx vs. late/any line trials (46.4% vs 70.4%; p<0.0003). In the metastatic setting, the median ORR for BioRx vs non-BioRx was 26.0% vs 44.2% (p<0.001). However, neither mean of medians for TTP (6.9 mo vs 7.5 mo; p=0.48) nor OS (19.6 mo vs 19.9 mo; p=0.51) were different for BioRx vs non-BioRx. Among metastatic BCT with single agent BioRx, median ORR = 6.0%, (interquartile range 1.4%-18.0%), TTP = 2.4 mo (interquartile range 1.8-5.5 mo), OS = 13.0 mo (interquartile range 6.9 -16.8 mo). Among all BioRx trials, 35.9% report no hematologic grade III/IV toxicity and 6.4% report no grade III/IV non-hematologic toxicity. Absence of grade III/IV hematologic toxicity was more common among single agent BioRx vs. combination BioRx (61.1% vs. 19%, p < 0.001). CONCLUSIONS: BioRx were used in 1/3 of recently published phase II BCTs. As single agents, BioRx often have reduced toxicity, but efficacy is highly variable. While median reported ORR for all BioRx trials is lower than that for other interventions, TTP and OS appear similar, supporting the belief that ORR may not be the optimal measure of BioRx efficacy.
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- Oncology & Carcinogenesis
- 1112 Oncology and Carcinogenesis
- 1103 Clinical Sciences
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Published In
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Oncology & Carcinogenesis
- 1112 Oncology and Carcinogenesis
- 1103 Clinical Sciences