Adherence to oral therapies among patients with renal cell carcinoma: Post hoc analysis of the ECOG-ACRIN E2805 trial

Caitlin C Murphy, Hannah M Fullington, David E Gerber, Isaac Alex Bowman, Maneka Puligandla, Janice P Dutcher, Robert S DiPaola, Naomi B Haas, Caitlin C Murphy, Hannah M Fullington, David E Gerber, Isaac Alex Bowman, Maneka Puligandla, Janice P Dutcher, Robert S DiPaola, Naomi B Haas

Abstract

Background: As use of oral cancer therapies increases, patient adherence has become critical when evaluating the effectiveness of therapy. In a phase III trial for renal cell carcinoma, we: (a) characterized adherence to sorafenib, sunitinib, and/or placebo and (b) identified factors associated with non-adherence.

Methods: ECOG-ACRIN E2805 was a double-blind, placebo-controlled, randomized trial comparing adjuvant sorafenib or sunitinib in patients with resected primary renal cell carcinoma at high risk for recurrence. We used patient-completed pill diaries to measure adherence as the number of pills taken divided by the number of pills prescribed. Log-binomial regression was used to identify correlates of non-adherence (<80% of prescribed pills reported as taken).

Results: Mean adherence was 90.7% among those assigned to sunitinib (n = 613) and 84.8% among those assigned to sorafenib (n = 616). Among those assigned to placebo, mean adherence was 94.9% and 92.4% to sunitinib and sorafenib placebo, respectively. Non-adherence was associated with race/ethnicity (non-Hispanic Black: prevalence ratio [PR] 2.22, 95% CI 1.63, 3.01; Hispanic: PR 1.54, 95% CI 1.05, 2.26), high volume enrollment (≥10 patients: PR 1.30, 95% CI 1.03, 1.64), treatment group (sunitinib: PR 2.24, 95% CI 1.66, 3.02; sorafenib: PR 2.37, 95% CI 1.74, 3.22), and skin rash (PR 1.36, 95% CI 1.03, 1.80).

Conclusion: Among patients participating in a randomized clinical trial, adherence to oral cancer therapies was lower compared to placebo. Adherence was also worse in racial/ethnic minorities, those experiencing toxicities, and high volume enrolling sites. Our findings highlight several challenges to address in clinical practice as use of oral therapies continues to increase.

Clinical trial registration number: This trial is registered with ClinicalTrials.gov, number NCT00326898.

Keywords: adherence; clinical trial; renal cell carcinoma.

Conflict of interest statement

Caitlin C. Murphy: Conuslting or advisory role: Freenome. Naomi B. Haas: Consulting or advisory role: Pfizer, Merck Sharp & Dohme; Expert testimony: Eli Lilly (immediate family member). David E. Gerber: Stock and other ownership interests: Gilead Sciences, Consulting or advisory role: Samsung Bioepis, Catalyst Pharmaceutical; Research funding: Astra‐Zeneca, BerGenBio, and Karyopharm. Isaac Alex Bowman: Consulting or advisory role: Foundation Medicine, Inc., Dendreon. Janice P. Dutcher: Consulting or advisory role: Eisai, Merck, Nektar, Amgen, Bristol Myers Squibb, Iovance, Clinigen. No other authors have financial disclosures or potential conflict of interest to report.

© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Forest plot of adjusted prevalence ratios, factors associated with non‐adherence (

FIGURE 2

Cumulative incidence of death (A)…

FIGURE 2

Cumulative incidence of death (A) and recurrence (B) by adherence to study drug,…

FIGURE 2
Cumulative incidence of death (A) and recurrence (B) by adherence to study drug, ECOG‐ACRIN E2805 (n = 1,858)
FIGURE 2
FIGURE 2
Cumulative incidence of death (A) and recurrence (B) by adherence to study drug, ECOG‐ACRIN E2805 (n = 1,858)

References

    1. Krzyzanowska MK, Powis M. Extending the quality and safety agenda from parenteral to oral chemotherapy. J Oncol Practice. 2015;11(3):198‐201.
    1. Goodin S, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Practice. 2011;7(1):7‐12.
    1. Neuss M, Gilmore T, Belderson K, et al. 2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, including standards for pediatric oncology. Oncol Nurs Forum. 2017;44(1):31‐43.
    1. Weingart SN, Brown E, Bach PB, et al. NCCN task force report: oral chemotherapy. J Natl Comprehensive Cancer Network: JNCCN. 2008;6(Suppl 3):S1‐14.
    1. Murphy CC, Fullington HM, Alvarez CA, et al. Polypharmacy and patterns of prescription medication use among cancer survivors. Cancer. 2018;124(13):2850‐2857.
    1. Segal EM, Flood MR, Mancini RS, et al. Oral chemotherapy food and drug interactions: a comprehensive review of the literature. J Oncol Practice. 2014;10(4):e255‐e268.
    1. Haas NB, Manola J, Uzzo RG, et al. Adjuvant sunitinib or sorafenib for high‐risk, non‐metastatic renal‐cell carcinoma (ECOG‐ACRIN E2805): a double‐blind, placebo‐controlled, randomised, phase 3 trial. Lancet. 2016;387(10032):2008‐2016.
    1. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134(2):459‐478.
    1. Ruddy KJ, Pitcher BN, Archer LE, et al. Persistence, adherence, and toxicity with oral CMF in older women with early‐stage breast cancer (Adherence Companion Study 60104 for CALGB 49907). Annals Oncol. 2012;23(12):3075‐3081.
    1. Partridge AH, Archer L, Kornblith AB, et al. Adherence and persistence with oral adjuvant chemotherapy in older women with early‐stage breast cancer in CALGB 49907: adherence companion study 60104. J Clin Oncol. 2010;28(14):2418‐2422.
    1. Mayer EL, Partridge AH, Harris LN, et al. Tolerability of and adherence to combination oral therapy with gefitinib and capecitabine in metastatic breast cancer. Breast Cancer Res Treat. 2009;117(3):615‐623.
    1. Makubate B, Donnan PT, Dewar JA, Thompson AM, McCowan C. Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer. 2013;108(7):1515‐1524.
    1. McCowan C, Shearer J, Donnan PT, et al. Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. Br J Cancer. 2008;99(11):1763‐1768.
    1. McCowan C, Wang S, Thompson AM, Makubate B, Petrie DJ. The value of high adherence to tamoxifen in women with breast cancer: a community‐based cohort study. Br J Cancer. 2013;109(5):1172‐1180.
    1. Marin D, Bazeos A, Mahon F‐X, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381‐2388.
    1. Hershman DL, Shao T, Kushi LH, et al. Early discontinuation and non‐adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126(2):529‐537.
    1. Lee S‐H, Bang Y‐J, Mainwaring P, et al. Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation analysis for safety and efficacy. Asia Pac J Clin Oncol. 2014;10(3):237‐245.
    1. Kim HR, Park HS, Kwon WS, et al. Pharmacogenetic determinants associated with sunitinib‐induced toxicity and ethnic difference in Korean metastatic renal cell carcinoma patients. Cancer Chemother Pharmacol. 2013;72(4):825‐835.
    1. Liu X, Fiocco M, Swen JJ, Guchelaar HJ. Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta‐analysis. Acta Oncologica (Stockholm, Sweden). 2017;56(4):582‐589.
    1. Wheeler SB, Spencer J, Pinheiro LC, et al. Endocrine therapy nonadherence and discontinuation in black and white women. J Natl Cancer Inst. 2019;111(5):498‐508.
    1. Elk R, Landrine H. Cancer disparities: causes and evidence‐based solutions. New York, NY: Springer Publishing Company; 2012.
    1. Bishop WP, Craddock Lee SJ, Skinner CS, Jones TM, McCallister K, Tiro JA. Validity of single‐item screening for limited health literacy in English and Spanish speakers. Am J Public Health. 2016;106(5):889‐892.
    1. Dusetzina SB, Winn AN, Abel GA, Huskamp HA, Keating NL. Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol. 2014;32(4):306‐311.
    1. Olszewski AJ, Dusetzina SB, Eaton CB, Davidoff AJ, Trivedi AN. Subsidies for oral chemotherapy and use of immunomodulatory drugs among medicare beneficiaries with myeloma. J Clin Oncol. 2017;35(29):3306–3314.
    1. Winn AN, Keating NL, Dusetzina SB. Factors associated with tyrosine kinase inhibitor initiation and adherence among medicare beneficiaries with chronic myeloid leukemia. J Clin Oncol. 2016;34(36):4323‐4328.
    1. Regnier Denois V, Poirson J, Nourissat A, Jacquin JP, Guastalla JP, Chauvin F. Adherence with oral chemotherapy: results from a qualitative study of the behaviour and representations of patients and oncologists. Eur J Cancer Care (Engl). 2011;20(4):520‐527.
    1. Murphy CC, Lee SJC, Gerber DE, Cox JV, Fullington HM, Higashi RT. Patient and provider perspectives on delivery of oral cancer therapies. Patient Educ Couns. 2019;102(11):2102‐2109.
    1. Basch E, Wood WA, Schrag D, et al. Feasibility and clinical impact of sharing patient‐reported symptom toxicities and performance status with clinical investigators during a phase 2 cancer treatment trial. Clin Trials (London, England). 2016;13(3):331‐337.
    1. Mallick R, Cai J, Wogen J. Predictors of non‐adherence to systemic oral therapy for advanced hepatocellular carcinoma. Curr Med Res Opin. 2013;29(12):1701‐1708.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する