TY - JOUR
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
N1 - Funding Information:
Conflict of interest Debu Tripathy has received remuneration from Novartis and serves in a consultant/advisory role for Novartis, Pfizer, and Nektar. Maura N. Dickler serves in a consultant/advisory role for Genentech/Roche, Pfizer, Novartis, Eli Lilly, AstraZeneca, TapIm-mune, and GI Therapeutics. Arti Hurria serves in a consultant/advisory role for Pierian Biosciences and MJH Healthcare Holdings, LLC and has received funding from Celgene and Novartis.
Funding Information:
Funding Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), P30CA033572, U10CA180790, U10CA180795, U10CA180820, U10CA180836, U10CA180838, U10CA180857, U10CA180858, U10CA180867, U10CA180888, and CA180858. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CALGB/Alliance 40503 was supported in part by Genentech and by a grant from The Breast Cancer Research Foundation.
Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/9/1
Y1 - 2018/9/1
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
KW - Breast cancer
KW - Risk factors
KW - Toxicity
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U2 - 10.1007/s10549-018-4828-5
DO - 10.1007/s10549-018-4828-5
M3 - Article
C2 - 29789969
AN - SCOPUS:85051072444
VL - 171
SP - 325
EP - 334
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -