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. 2018 Oct;119(8):922-927.
doi: 10.1038/s41416-018-0290-8. Epub 2018 Oct 15.

Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre

Brent O'Carrigan  1 , Joline Si Jing Lim  1   2 , Awais Jalil  1 , Samuel John Harris  1 , Dionysis Papadatos-Pastos  1 , Udai Banerji  1   3 , Juanita Lopez  1   3 , Johann Sebastian de Bono  1   3 , Timothy Anthony Yap  4   5
Affiliations

Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre

Brent O'Carrigan et al. Br J Cancer. 2018 Oct.

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Mutational landscape from targeted amplicon NGS profiling of patients differs by histologic subtype. The number and proportion of participants with mutations identified in the listed genes are shown by histologic subtype TNBC and non-TNBC. TNBC triple-negative breast cancer
Fig. 2
Fig. 2
a Clinical benefit rate (CBR) and b partial response (PR) rate among participants on matched vs non-matched trials. Two-sided χ2 test
Fig. 3
Fig. 3
a Progression-free survival (PFS) and b overall survival (OS) among participants of matched vs non-matched trials from the first administration of study agent for each trial encounter. Kaplan–Meier survival analysis with log-rank (Mantel–Cox) test and hazard ratio (HR)
See this image and copyright information in PMC

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