TY - JOUR
T1 - Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre
AU - O’Carrigan, Brent
AU - Lim, Joline Si Jing
AU - Jalil, Awais
AU - Harris, Samuel John
AU - Papadatos-Pastos, Dionysis
AU - Banerji, Udai
AU - Lopez, Juanita
AU - de Bono, Johann Sebastian
AU - Yap, Timothy Anthony
N1 - Publisher Copyright:
© 2018, Cancer Research UK.
PY - 2018/10/16
Y1 - 2018/10/16
N2 - 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.
AB - 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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U2 - 10.1038/s41416-018-0290-8
DO - 10.1038/s41416-018-0290-8
M3 - Article
C2 - 30318518
AN - SCOPUS:85054926259
SN - 0007-0920
VL - 119
SP - 922
EP - 927
JO - British journal of cancer
JF - British journal of cancer
IS - 8
ER -