Preferences for Chemotherapy Discontinuation due to Chemotherapy-Induced Peripheral Neuropathy Among Patients with Metastatic Breast Cancer

Abstract

Background: Women with breast cancer often describe chemotherapy-induced peripheral neuropathy (CIPN) as one of the most distressing treatment-related symptoms, significantly affecting their function and quality of life. The progression of CIPN can, in some cases, lead to treatment discontinuation, potentially compromising the effectiveness of therapies for patients with metastatic breast cancer (mBC). Clinical guidelines offer limited guidance on when to discontinue treatment, making it crucial to incorporate patient preferences into shared decision-making processes. Despite the importance of seeking patients’ input, the extent to which patients are willing to tolerate CIPN symptoms and the factors that influence their decision to discontinue treatment remain unknown. Therefore, this dissertation aimed to measure preferences among patients with mBC in the context of treatment discontinuation due to CIPN. Methods: An online survey, incorporating both a best-worst scaling (BWS) and a discrete-choice experiment (DCE), was created through a comprehensive 5-stage process, which included evidence synthesis, consultation with clinicians (n=3), engagement with patients (n=7), pretesting (n=20), and pilot testing (n=61). The refined final survey was subsequently distributed to women who had mBC and CIPN. In the BWS, respondents viewed repeated subsets of objects and were required to select the most and least important factors that influenced their decision to discontinue treatment. For the DCE, participants were presented with various scenarios that involved different levels of risks and benefits, and they had to choose their preferred scenario. The priorities and preferences obtained from both the BWS and DCE were analyzed using effects coding and the conditional logit model. Results: A total of 189 respondents completed the survey. Seven objects were incorporated into the BWS: relieving current neuropathy symptoms, reducing risk of long-term neuropathy, having another cancer treatment option, understanding the risk of treatment discontinuation, and receiving support for treatment discontinuation from the oncologist, loved ones, or patients with similar experiences. Four risk-benefit attributes were incorporated in the DCE: progression-free survival (6, 12, 24 months), neuropathy in hands (mild, moderate, severe), neuropathy in feet (mild, moderate, severe), and neuropathy persistence (short-term, long-term, permanent). The BWS results showed that when patients were faced with the decision to discontinue treatment because of CIPN, respondents prioritized having another cancer treatment option the most (coefficient=0.96, SE=0.06). Patients also highly prioritized understanding the risk of treatment discontinuation (coefficient=0.61, SE=0.06), followed by reducing risk of long-term neuropathy (coefficient=0.60, SE=0.06), and relieving current neuropathy symptoms (coefficient=0.38, SE=0.06). Support from the oncologist (coefficient=0.07, SE=0.05), loved ones (coefficient=-1.07, SE=0.06) and other patients (coefficient=-1.55, SE=0.07) were prioritized the least. The DCE found that higher preference weights for attribute levels were associated with better clinical outcomes or lower harm. Regarding the relative attribute importance (RAI), progression-free survival (RAI=34.03%) and neuropathy persistence (RAI=34.03%) were the most important attributes, followed by neuropathy in hands (RAI=24.37%), and feet (RAI=7.56%). Respondents required a minimum of 2.80, 6.65, and 9.30 additional months of progression-free survival to accept a one-level increase in the severity of neuropathy in the hands or feet, and in the duration of neuropathy persistence, respectively. Conclusions: Prolonging progression-free survival and reducing the risk of neuropathy persistence were the primary factors driving patient priorities and preferences when considering treatment discontinuation. Patients were less willing to tolerate CIPN risk if it becomes long-term or permanent. These findings offer valuable insights for clinicians when discussing CIPN treatment discontinuation with their patients. Clinicians should educate patients about the risks associated with treatment discontinuation, the potential for long-term CIPN, and alternative, less neurotoxic cancer treatment options.