US food and drug administration pooled analysis to assess the impact of bone-only metastatic breast cancer on clinical trial outcomes and radiographic assessments

Suparna B. Wedam, Julia Beaver, Laleh Amiri-Kordestani, Erik Bloomquist, Shenghui Tang, Kirsten B. Goldberg, Rajeshwari Sridhara, Amna Ibrahim, Geoffrey Kim, Paul Kluetz, Amy McKee, Richard Pazdur

Research output: Contribution to journalArticle

Abstract

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5%(range: 4%to 26%), dependent on subtype. Investigator-assessed progressionfree survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBMPFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

Original languageEnglish (US)
Pages (from-to)1225-1231
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number12
DOIs
StatePublished - Apr 20 2018
Externally publishedYes

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United States Food and Drug Administration
Outcome Assessment (Health Care)
Clinical Trials
Breast Neoplasms
Bone and Bones
Neoplasm Metastasis
Survival
Research Personnel
Bone Diseases
Licensure
Biological Products
Natural History

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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US food and drug administration pooled analysis to assess the impact of bone-only metastatic breast cancer on clinical trial outcomes and radiographic assessments. / Wedam, Suparna B.; Beaver, Julia; Amiri-Kordestani, Laleh; Bloomquist, Erik; Tang, Shenghui; Goldberg, Kirsten B.; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Kluetz, Paul; McKee, Amy; Pazdur, Richard.

In: Journal of Clinical Oncology, Vol. 36, No. 12, 20.04.2018, p. 1225-1231.

Research output: Contribution to journalArticle

Wedam, SB, Beaver, J, Amiri-Kordestani, L, Bloomquist, E, Tang, S, Goldberg, KB, Sridhara, R, Ibrahim, A, Kim, G, Kluetz, P, McKee, A & Pazdur, R 2018, 'US food and drug administration pooled analysis to assess the impact of bone-only metastatic breast cancer on clinical trial outcomes and radiographic assessments', Journal of Clinical Oncology, vol. 36, no. 12, pp. 1225-1231. https://doi.org/10.1200/JCO.2017.74.6917
Wedam, Suparna B. ; Beaver, Julia ; Amiri-Kordestani, Laleh ; Bloomquist, Erik ; Tang, Shenghui ; Goldberg, Kirsten B. ; Sridhara, Rajeshwari ; Ibrahim, Amna ; Kim, Geoffrey ; Kluetz, Paul ; McKee, Amy ; Pazdur, Richard. / US food and drug administration pooled analysis to assess the impact of bone-only metastatic breast cancer on clinical trial outcomes and radiographic assessments. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 12. pp. 1225-1231.
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abstract = "Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49{\%} (range: 42{\%} to 73{\%}) of patients across trials. BO disease was present in 12.5{\%}(range: 4{\%}to 26{\%}), dependent on subtype. Investigator-assessed progressionfree survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95{\%} CI, 0.591 to 0.696; BO v NBMPFS HR, 0.70; 95{\%} CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95{\%} CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95{\%} CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.",
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T1 - US food and drug administration pooled analysis to assess the impact of bone-only metastatic breast cancer on clinical trial outcomes and radiographic assessments

AU - Wedam, Suparna B.

AU - Beaver, Julia

AU - Amiri-Kordestani, Laleh

AU - Bloomquist, Erik

AU - Tang, Shenghui

AU - Goldberg, Kirsten B.

AU - Sridhara, Rajeshwari

AU - Ibrahim, Amna

AU - Kim, Geoffrey

AU - Kluetz, Paul

AU - McKee, Amy

AU - Pazdur, Richard

PY - 2018/4/20

Y1 - 2018/4/20

N2 - Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5%(range: 4%to 26%), dependent on subtype. Investigator-assessed progressionfree survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBMPFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

AB - Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5%(range: 4%to 26%), dependent on subtype. Investigator-assessed progressionfree survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBMPFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

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