Hadar Goldvaser1, Domen Ribnikar2, Rouhi Fazelzad3, Bostjan Seruga4, Arnoud J Templeton5, Alberto Ocana6, Eitan Amir7. 1. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada; Sackler Faculty of Medicine, Tel Aviv University, POB 39040, Tel Aviv 6997801, Israel. Electronic address: hadar7g@gmail.com. 2. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada. Electronic address: domen.ribnikar@uhn.ca. 3. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada. Electronic address: Rouhi.Fazelzad@uhn.ca. 4. Department of Medical Oncology, Institute of Oncology Ljubljana, 2 Zaloska cesta, Ljubljana 1000, Slovenia. Electronic address: BSeruga@onko-i.si. 5. Department of Oncology and Hematology, St. Claraspital, Faculty of Medicine, University of Basel, Kleinriehenstrasse 30, Basel 4058, Switzerland. Electronic address: arnoud.templeton@unibas.ch. 6. Translational Research Unit, Centro Regional de Investigaciones Biomedicas Universidad de Castilla La Mancha, Albacete University Hospital, calle Francisco Javier de Moya 02006, Albacete, Spain. Electronic address: albertocana@yahoo.es. 7. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada. Electronic address: eitan.amir@uhn.ca.
Abstract
BACKGROUND: The presence of non-measurable disease is common in metastatic breast cancer. It is unknown whether treatment effect on progression free survival (PFS) is consistent among patients with measurable and non-measurable disease. METHODS: A systematic literature search identified phase III randomized controlled trials (RCTs) in metastatic breast cancer that reported outcomes in patients with non-measurable and measurable disease. Hazard ratios (HRs) and 95% confidence intervals were computed to compare the individual trial treatment effect on PFS in non-measurable versus measurable disease. Analyses were repeated for bone-only compared to non-bone-only disease and based on drug mechanism of action. RESULTS: Among 82 RCTs that enrolled patients with non-measurable disease, data were available from 16 trials comprising 8516 patients. Treatment effect on PFS was similar in patients with non-measurable and measurable disease (HR for intra-study comparison=1.01, p=0.82). However, compared to non-bone-only disease, a significantly greater effect on PFS was seen in those with bone-only disease (HR 0.83, p=0.03). Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, p=0.01) and a lesser effect on PFS in RCTs of antiangiogenic drugs (HR 1.34, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy (HR 1.13, p=0.23) and chemotherapy (HR 0.73, p=0.22). CONCLUSIONS: There is variability in treatment effect on PFS in patients with measurable and non-measurable disease, especially those with bone-only disease. Standardization of PFS determination in these patients is warranted.
BACKGROUND: The presence of non-measurable disease is common in metastatic breast cancer. It is unknown whether treatment effect on progression free survival (PFS) is consistent among patients with measurable and non-measurable disease. METHODS: A systematic literature search identified phase III randomized controlled trials (RCTs) in metastatic breast cancer that reported outcomes in patients with non-measurable and measurable disease. Hazard ratios (HRs) and 95% confidence intervals were computed to compare the individual trial treatment effect on PFS in non-measurable versus measurable disease. Analyses were repeated for bone-only compared to non-bone-only disease and based on drug mechanism of action. RESULTS: Among 82 RCTs that enrolled patients with non-measurable disease, data were available from 16 trials comprising 8516 patients. Treatment effect on PFS was similar in patients with non-measurable and measurable disease (HR for intra-study comparison=1.01, p=0.82). However, compared to non-bone-only disease, a significantly greater effect on PFS was seen in those with bone-only disease (HR 0.83, p=0.03). Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, p=0.01) and a lesser effect on PFS in RCTs of antiangiogenic drugs (HR 1.34, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy (HR 1.13, p=0.23) and chemotherapy (HR 0.73, p=0.22). CONCLUSIONS: There is variability in treatment effect on PFS in patients with measurable and non-measurable disease, especially those with bone-only disease. Standardization of PFS determination in these patients is warranted.