medwireNews: Toxicity Index (TI) data plus patient-reported outcomes (PROs) may provide greater insights into reasons for early discontinuation of endocrine therapy than maximum-grade adverse event (AE) data alone, US study findings indicate.
The secondary analysis of the randomized, double-blind NSABP B-35 trial revealed that 28.5% of the 3046 participants discontinued tamoxifen 20 mg/day or anastrozole 1 mg/day before the end of the 5-year study for reasons other than treatment completion, disease progression, or death.
All of the women included in the study were postmenopausal with ductal carcinoma in situ that had been treated with breast-conserving therapy.
N Lynn Henry (University of Michigan Rogel Cancer Center, Ann Arbor) and co-investigators describe the TI as “a summary score that considers the frequency and severity of AEs and reflects the impact of multiple toxicities experienced by an individual patient over time.”
In a multivariate analysis that incorporated baseline characteristics and individual AEs from the TI, the team found that sensory neuropathy, myalgia, fatigue, myocardial ischemia or infarction, and arthralgia were each associated with a significantly increase likelihood of discontinuation of both tamoxifen and anastrozole.
In addition, thrombosis, nausea, transaminitis, dizziness, chest pain, and headache were each, in order of significance, associated with tamoxifen discontinuation, whereas cerebrovascular ischemia, anorexia, pruritis, and bone pain were significantly associated with anastrozole discontinuation.
The researchers then incorporated baseline PRO data from 1194 participants into the analysis, reasoning that “the baseline PRO data could identify pretreatment patient symptoms affecting subsequent toxicity.”
In this case, thromboembolism and arthralgia were the only AEs significantly associated with early discontinuation of both drugs, with other AEs linked to discontinuation varying by treatment.
The only PROs significantly associated with early discontinuation of tamoxifen were baseline pain interference, hot flashes, and unhappiness, while hot flashes were associated with anastrozole discontinuation.
Writing in the Journal of Clinical Oncology, Henry et al conclude that their study “identified both anticipated and unanticipated toxicities associated with treatment discontinuation.”
They say: “These findings may be clinically useful for a priori identification of patients who will have difficulty tolerating an [endocrine therapy], including both preexisting symptoms that may predispose patients to an increased risk of treatment discontinuation and treatment-emergent symptoms that may require proactive intervention.”
The authors add that using the TI and PROs to assess treatment tolerability ”should be considered both when analyzing and interpreting data from previously conducted [randomized controlled trials] and when designing prospective studies examining new treatment interventions for patients with cancer.”
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J Clin Oncol 2021; doi:10.1200/JCO.21.00910