In an analysis from the NRG Oncology/NSABP B-35 trial reported in the Journal of Clinical Oncology, N. Lynn Henry, MD, PhD, and colleagues identified toxicity and patient-reported outcome factors associated with early discontinuation of adjuvant endocrine therapy in women with ductal carcinoma in situ.
As stated by the investigators, “The U.S. National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event and patient-reported outcome questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastrozole and tamoxifen discontinuation.”
N. Lynn Henry, MD, PhD
Study Details
In the trial, 3,104 postmenopausal women with ductal carcinoma in situ treated with breast-conserving therapy were randomly assigned to receive anastrozole or tamoxifen for 5 years. The primary outcome measure for the current analysis was time to treatment discontinuation.
Adverse events were collected every 6 months from random assignment for all 3,104 patients and summarized using the Toxicity Index. Patient-reported outcome data were collected using several questionnaires at baseline and every 6 months from 1,194 patients.
Key Findings
Among 3,046 patients with sufficient data for analysis, 869 (28.5%) discontinued treatment prematurely, including 429 (28.2%) receiving tamoxifen and 440 (28.9%) receiving anastrozole.
Toxicity Index analysis showed that toxicity was significantly associated with early discontinuation of both tamoxifen (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.65–1.90) and anastrozole (HR = 1.71, 95% CI = 1.60–1.83). On multivariate analysis for individual adverse events, fatigue, arthralgia, myalgia, sensory neuropathy, and cardiac ischemia were associated with early discontinuation for both drugs. Additional adverse events associated with early discontinuation were thrombosis, nausea, transaminitis, dizziness, chest pain, and headache for tamoxifen, and anorexia, cerebrovascular ischemia, pruritus, and bone pain for anastrozole.
On multivariate analysis, patient-reported outcomes during treatment that were significantly associated with early discontinuation consisted of worse physical function and depression for tamoxifen and worse physical function for anastrozole. Patient-reported outcomes at baseline that were significantly associated with early discontinuation consisted of pain interference, hot flashes, and unhappiness for tamoxifen, and hot flashes for anastrozole.
The investigators concluded: “Analysis of adverse events using the Toxicity Index yielded important insights into reasons for discontinuation of endocrine therapy that was enhanced by the addition of patient-reported outcome baseline and treatment-emergent symptoms.”
Dr. Henry, of the University of Michigan Rogel Cancer Center, Ann Arbor, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and the National Institutes of Health. For full disclosures of the study authors, visit ascopubs.org.
