Quantifying Treatment Tolerability in Real-world Breast Cancer Practice: A Pragmatic Approach Utilizing Patient-Reported Outcomes (PROs)

Authors: Emelly Rusli MPH, Aaron Galaznik MD MBA, Debra Wujcik PhD RN Carevive by HealthCatalystTM, Boston, MA

Background

• Treatment tolerability in cancer care, historically assessed by the clinician, is moving towards incorporating patients’ voices to capture how they feel and function during treatment^1-3.
• Women undergoing breast cancer (BC) treatment often experience debilitating symptoms and decreased quality-of-life (QoL)⁴.
• Patient-reported outcomes (PROs) collected from remote symptom monitoring (RSM) enable early identification of patients with poor functional status⁵ and provide insights on tolerability from patients’ perspectives.
• Measurement of comparative patient-reported tolerability (PRT) for thyroid cancer was recently published by Brose et al. (2024)⁶.
• This study aimed to adopt this novel method to explore PRT in breast cancer using PROs collected in real-world clinical practice.

Methods

• Study cohort included patients enrolled in Carevive PROmpt®, an RSM platform, and received treatment for BC anytime between 9/2020 and 5/2024 (study period).
• Patients completed at least one weekly PRO survey that included treatment bother, measured by a single item FACT-GP5* (“I am bothered by side effects of treatment”), and were followed from baseline survey completion until the last survey completion or end of study period (follow-up period). Follow-up period occurred while patients received BC treatment.
• Treatment data (name, start, and end dates) were sourced from the electronic medical record or entered directly into the platform by the care team.
• PRT was assessed using the method developed by Brose et al. (2024)6 with the below modifications:
  • The use of follow-up time to calculate PRT due to variable follow-up period among patients
  • The semantic change (e.g., “high treatment bother” instead of “high side-effect burden”) given the heterogeneity of treatments received during the follow-up period
  • The term “persistent high treatment bother” (high treatment bother reported 76-100% of the time) was added by authors of this study
• Results were explored by stage, biomarker status, therapy type, and PRO assessment time. No statistical comparison was conducted in the study.
• Treatment tolerability was defined as the degree of treatment bother and was classified into two categories based on the response to the single item FACT-GP5* on a given survey:
  • High treatment bother (HTB), defined as response 3 (“Quite a bit”) or 4 (“Very much”)
  • Low treatment bother (LTB), defined as response 0 (“Not at all”), 1 (“A little bit”), or 2 (“Somewhat”)
• Patient-reported tolerability (PRT) was calculated as the proportion of time with high treatment bother during the follow-up period (0-25%, 26-50%, 51-75%, 76-100%).
  • Persistent high treatment bother was defined as high treatment bother being reported 76-100% of the time during the follow-up period.

Conclusions

• This study used PROs to quantify treatment tolerability in women receiving BC therapy in the real-world clinical practice.
• Nearly half of patients reported HTB at least once and more than 20% of patients reported HTB for at least half of their follow-up duration.
• While most patients reported HTB for a small fraction of their time, for 10% of patients, the time with HTB was about 95% of their time during follow-up.
• A closer look showed more patients with metastatic disease, TNBC type, and targeted therapy reported persistent HTB. Persistent HTB was also higher at week 5+ versus week 1-4.
• PRT provides the means to quantify tolerability and track longitudinal changes, which gives insights into patient monitoring at various points of BC treatment journey.
• Future studies should focus on factors that impact tolerability, symptom persistence, and impact of symptom management across BC therapy types to overall QoL.

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References

1. Kluetz, P. G., Kanapuru, B., Lemery, S., et al. (2018). Informing the Tolerability of Cancer Treatments Using Patient-Reported Outcome Measures: Summary of an FDA and Critical Path Institute Workshop. Value in health, 21(6), 742–747. https://doi. org/10.1016/j.jval.2017.09.009

2. Basch E., Campbell A., Hudgens S., et al. (2020). Broadening the definition of tolerability in cancer clinical trials to better measure the patient experience [White Paper]. Friends of Cancer. Washington DC.

3. Peipert, J. D., Smith, M. L., & EVOLV Study Team (2022). Reconsidering tolerability of cancer treatments: opportunities to focus on the patient. Supportive care in cancer, 30(5), 3661–3663. https://doi. org/10.1007/s00520-021-06700-0

4. Hamer, J., McDonald, R., Zhang, L., Verma, S., Leahey, A., Ecclestone, C., Bedard, G., Pulenzas, N., Bhatia, A., Chow, R., DeAngelis, C., Ellis, J., Rakovitch, E., Lee, J., & Chow, E. (2017). Quality of life (QOL) and symptom burden (SB) in patients with breast cancer. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 25(2), 409–419. https://doi. org/10.1007/s00520-016-3417-6

5. Rusli, E., Wujcik, D., & Galaznik, A. (2024). Remote Symptom Alerts and Patient- Reported Outcomes (PROS) in Real- World Breast Cancer Practice: Innovative Data to Derive Symptom Burden and Quality of Life. Bioengineering (Basel, Switzerland), 11(8), 846. https://doi. org/10.3390/bioengineering11080846

6. Brose M.S., et al. (2024). Comparative patient-reported tolerability (PRT): A multiplicity-controlled analysis of LIBRETTO-531, a randomized controlled trial (RCT) in medullary thyroid cancer (MTC). JCO, 42, 11111-11111. doi:10.1200/ JCO.2024.42.16_suppl.11111