Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole

a CALGB 40503 (alliance) correlative study

Daneng Li, Linda M. McCall, Olwen M. Hahn, Clifford A. Hudis, Harvey J. Cohen, Hyman B. Muss, Aminah Jatoi, Jacqueline M. Lafky, Karla V. Ballman, Eric P. Winer, Debu Tripathy, Bryan Schneider, William Barry, Maura N. Dickler, Arti Hurria

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. Methods: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. Results: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events. Conclusions: Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.

Original languageEnglish (US)
Pages (from-to)325-334
Number of pages10
JournalBreast Cancer Research and Treatment
Volume171
Issue number2
DOIs
StatePublished - Sep 1 2018

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letrozole
Hormones
Breast Neoplasms
Incidence
Logistic Models
Aptitude
National Cancer Institute (U.S.)
Bevacizumab
Nutritional Status
Proteinuria
Terminology
Social Support

Keywords

  • Bevacizumab
  • Breast cancer
  • Risk factors
  • Toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole : a CALGB 40503 (alliance) correlative study. / Li, Daneng; McCall, Linda M.; Hahn, Olwen M.; Hudis, Clifford A.; Cohen, Harvey J.; Muss, Hyman B.; Jatoi, Aminah; Lafky, Jacqueline M.; Ballman, Karla V.; Winer, Eric P.; Tripathy, Debu; Schneider, Bryan; Barry, William; Dickler, Maura N.; Hurria, Arti.

In: Breast Cancer Research and Treatment, Vol. 171, No. 2, 01.09.2018, p. 325-334.

Research output: Contribution to journalArticle

Li, D, McCall, LM, Hahn, OM, Hudis, CA, Cohen, HJ, Muss, HB, Jatoi, A, Lafky, JM, Ballman, KV, Winer, EP, Tripathy, D, Schneider, B, Barry, W, Dickler, MN & Hurria, A 2018, 'Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study', Breast Cancer Research and Treatment, vol. 171, no. 2, pp. 325-334. https://doi.org/10.1007/s10549-018-4828-5
Li, Daneng ; McCall, Linda M. ; Hahn, Olwen M. ; Hudis, Clifford A. ; Cohen, Harvey J. ; Muss, Hyman B. ; Jatoi, Aminah ; Lafky, Jacqueline M. ; Ballman, Karla V. ; Winer, Eric P. ; Tripathy, Debu ; Schneider, Bryan ; Barry, William ; Dickler, Maura N. ; Hurria, Arti. / Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole : a CALGB 40503 (alliance) correlative study. In: Breast Cancer Research and Treatment. 2018 ; Vol. 171, No. 2. pp. 325-334.
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abstract = "Background: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. Methods: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. Results: One hundred thirteen (58{\%}) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26{\%}), pain (20{\%}), and proteinuria (7{\%}). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events. Conclusions: Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.",
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T1 - Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole

T2 - a CALGB 40503 (alliance) correlative study

AU - Li, Daneng

AU - McCall, Linda M.

AU - Hahn, Olwen M.

AU - Hudis, Clifford A.

AU - Cohen, Harvey J.

AU - Muss, Hyman B.

AU - Jatoi, Aminah

AU - Lafky, Jacqueline M.

AU - Ballman, Karla V.

AU - Winer, Eric P.

AU - Tripathy, Debu

AU - Schneider, Bryan

AU - Barry, William

AU - Dickler, Maura N.

AU - Hurria, Arti

PY - 2018/9/1

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N2 - Background: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. Methods: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. Results: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events. Conclusions: Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.

AB - Background: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. Methods: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. Results: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events. Conclusions: Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.

KW - Bevacizumab

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KW - Risk factors

KW - Toxicity

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