Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre.
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Embargo End Date
Authors
O'Carrigan, B
Lim, JSJ
Jalil, A
Harris, SJ
Papadatos-Pastos, D
Banerji, U
Lopez, J
de Bono, JS
Yap, TA
Lim, JSJ
Jalil, A
Harris, SJ
Papadatos-Pastos, D
Banerji, U
Lopez, J
de Bono, JS
Yap, TA
Document Type
Other
Date
2018-10-15
Date Accepted
Abstract
Background Greater understanding of the molecular classification of breast cancer has permitted the development of rational drug design strategies. In a phase I clinical trial setting, molecular profiling with next-generation sequencing of individual tumour samples has been employed to guide treatment.Methods We conducted a retrospective evaluation of clinical outcomes of patients with metastatic breast cancer (MBC) treated in phase I clinical trials at our institution to assess the benefit of molecularly matched compared to non-matched treatments.Results A total of 97 consecutive patients with MBC were enrolled onto ≥1 trial between 2009 and 2015. Fourteen patients participated in multiple trials, and a total of 113 trial encounters were reviewed in this retrospective study. Eighty-three percent of patients with molecular data available were able to participate in trials matched to molecular aberrations. Patients who were treated on matched studies had improved clinical benefit (RR: 1.80, p = 0.005), progression-free (HR: 0.52, p = 0.003) and overall survival (HR: 0.54, p < 0.001). Treatment was well tolerated with low rates of treatment discontinuation for toxicity (8% overall) that did not differ between groups. No toxicity-related deaths were observed.Conclusions Molecular profiling for MBC patients in a phase I setting is feasible and aids therapeutic decisions with improved patient outcomes.
Citation
British journal of cancer, 2018, 119 (8), pp. 922 - 927
Source Title
Publisher
ISSN
0007-0920
eISSN
1532-1827
Collections
Research Team
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group