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Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03)

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Abstract

Purpose

Aromatase inhibitors are the most commonly prescribed adjuvant endocrine therapy for hormone-dependent early breast cancer in postmenopausal women. Among Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had comparable 5-year event-free survival. This companion study examined differences in patient-reported treatment-related symptoms (TRS) and health-related quality of life (HRQL) among postmenopausal women randomized to anastrozole or exemestane.

Methods

MA.27 participants (N = 686, of 7576) randomized to 5 years of anastrozole (1 mg/day, n = 371, Arm A) or exemestane (25 mg/day, n = 315, Arm E) completed the 56-item Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) questionnaire to assess TRS and HRQL. The FACT-ES was completed at baseline, 3, 6, 12, and 24 months.

Results

No significant differences in FACT-ES median scores measuring TRS and HRQL were observed between treatment arms at any time point. Change in TRS from baseline was statistically significant at 3, 6, 12, and 24 months. HRQL was stable over time in both arms. Greater TRS burden was associated with poorer HRQL (coefficient = 0.57, p < 0.001). Twenty percent of patients discontinued AI therapy by month 24 and 32% discontinued AIs at 4 years. In both arms, patients reporting more side effect bother prior to initiating study treatment had a higher risk of discontinuing treatment before completing protocol therapy (hazard ratio [HR] 1.29, 95% CI 1.08–1.55, p = 0.01).

Conclusions

TRS and HRQL were comparable between anastrozole and exemestane. TRS negatively affect HRQL. Women who report being bothered by treatment side effects prior to initiating an AI are at increased risk for early treatment discontinuation.

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Abbreviations

CCTG:

Canadian Clinical Trials Group

ECOG:

Eastern Cooperative Oncology Group

ACRIN:

American College of Radiology Imaging Network

TRS:

Treatment-related symptoms

HRQL:

Health-related quality of life

FACT-ES:

Functional Assessment of Cancer Therapy-Endocrine Symptoms

PRO:

Patient-reported outcomes

AIs:

Aromatase inhibitors

Arm A:

Anastrozole

Arm E:

Exemestane

References

  1. Baum M, Buzdar A, Cuzick J, Forbes J, Houghton J, Howell A, Sahmoud T, ATAC (Arimidex Tamoxifen Alone or in Combination) Trialists’ Group (2003) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 98(9):1802–1810

    Article  CAS  Google Scholar 

  2. Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, Buyse M, Baum M, Buzdar A, Colleoni M, Coombes C, Snowdon C, Gnant M, Jakesz R, Kaufmann M, Boccardo F, Godwin J, Davies C, Peto R (2010) Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol 28(3):509

    Article  PubMed  CAS  Google Scholar 

  3. Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D’Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE (2013) Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27—a randomized controlled phase III trial. J Clin Oncol 31(11):1398–1404. https://doi.org/10.1200/jco.2012.44.7805

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Stearns V, Chapman JA, Ma CX, Ellis MJ, Ingle JN, Pritchard KI, Budd GT, Rabaglio M, Sledge GW, Le Maitre A, Kundapur J, Liedke PE, Shepherd LE, Goss PE (2015) Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. J Clin Oncol 33(3):265–271. https://doi.org/10.1200/jco.2014.57.6926

    Article  PubMed  CAS  Google Scholar 

  5. Coates AS, Keshaviah A, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Lang I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 25(5):486–492. https://doi.org/10.1200/jco.2006.08.8617

    Article  PubMed  CAS  Google Scholar 

  6. Fallowfield L, Cella D, Cuzick J, Francis S, Locker G, Howell A (2004) Quality of life of postmenopausal women in the anastrozole, tamoxifen, alone or in combination adjuvant breast cancer trial. J Clin Oncol 22(21):4261–4271

    Article  PubMed  CAS  Google Scholar 

  7. Sestak I, Cuzick J, Sapunar F, Eastell R, Forbes JF, Bianco AR, Buzdar AU (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9(9):866–872. https://doi.org/10.1016/s1470-2045(08)70182-7

    Article  PubMed  Google Scholar 

  8. Fallowfield LJ, Kilburn LS, Langridge C, Snowdon CF, Bliss JM, Coombes RC, IES Trial Steering Committee (2012) Long-term assessment of quality of life in the Intergroup Exemestane Study: 5 years post-randomisation. Br J Cancer British Journal of Cancer 106(6):1063–1067

    Google Scholar 

  9. Basch E, Abernethy AP, Mullins CD, Reeve BB, Smith ML, Coons SJ, Sloan J, Wenzel K, Chauhan C, Eppard W, Frank ES, Lipscomb J, Raymond SA, Spencer M, Tunis S (2012) Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology. J Clin Oncol 15:15

    Google Scholar 

  10. Fromme EK, Eilers KM, Mori M, Hsieh YC, Beer TM (2004) How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the quality-of-life questionnaire C30. J Clin Oncol 22(17):3485–3490

    Article  PubMed  Google Scholar 

  11. Velikova G, Booth L, Smith AB, Brown PM, Lynch P, Brown JM, Selby PJ (2004) Measuring quality of life in routine oncology practice improves communication and patient well-being: a randomized controlled trial. J Clin Oncol 22(4):714–724

    Article  PubMed  Google Scholar 

  12. Basch E (2010) The missing voice of patients in drug-safety reporting. N Engl J Med 362(10):865–869

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Detmar SB, Aaronson N, Wever LD, Muller M, Schornagel JH (2000) How are you feeling? Who wants to know? Patients’ and oncologists’ preferences for discussing health-related quality of life issues. J Clin Oncol 18(18):3295–3301

    Article  PubMed  CAS  Google Scholar 

  14. Patrick DL, Burke LB, Powers JH, Scott JA, Rock EP, Dawisha S, O’Neill R, Kennedy DL (2007) Patient-reported outcomes to support medical product labeling claims: FDA perspective. Value Health 10(Suppl 2):S125–137. https://doi.org/10.1111/j.1524-4733.2007.00275.x

    Article  PubMed  Google Scholar 

  15. Cella D, Fallowfield L (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107(2):167–180

    Article  PubMed  CAS  Google Scholar 

  16. Ruddy K, Mayer E, Partridge A (2009) Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin 59(1):56–66. https://doi.org/10.3322/caac.20004

    Article  PubMed  Google Scholar 

  17. Cuzick J, Sestak I, Cella D, Fallowfield L (2008) Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol 9:1143–1147

    Article  PubMed  CAS  Google Scholar 

  18. Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D (1999) Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat 55(2):189–199

    Article  PubMed  CAS  Google Scholar 

  19. Wilcoxon F (1945) Individual comparisons by ranking methods. Biometrics 1:80–83

    Article  Google Scholar 

  20. Schluchter MD (1992) Methods for the analysis of informatively censored longitudinal data. Stat Med 11:1861–1870

    Article  PubMed  CAS  Google Scholar 

  21. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  22. Cox DR (1972) Regression models and life tables (with discussion). J R Stat Soc B 34:187–220

    Google Scholar 

  23. Anderson JR, Cain KC, Gelber RD (1983) Analysis of survival by tumor response. J Clin Oncol 1:710–719

    Article  PubMed  CAS  Google Scholar 

  24. StataCorp (2009) Stata statistical software: release 11. StataCorp LP, College Station

    Google Scholar 

  25. Pearman T, Beaumont J, Mroczek D, O’Connor M, Cella D (in press) Validity and utility of a single-item measure of patient-reported bother from side effects of cancer therapy. Cancer

Download references

Acknowledgements

This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following Award Numbers: CA189828, CA180867, CA189808, CA189954, CA180799, CA189822, CA189863, CA189860, CA189812, CA180816, CA180795, CA180863, Canadian Cancer Society Research Institute Grants #021039 and #704970 and by the AVON Breast Cancer Crusade ABCC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

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Authors and Affiliations

  1. Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27151, USA

    Lynne I. Wagner

  2. Dana Farber Cancer Institute, Boston, MA, USA

    Fengmin Zhao

  3. Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

    Paul E. Goss

  4. Canadian Cancer Trials Group (CCTG), Kingston, Canada

    Judith-Anne W. Chapman, Lois E. Shepherd & Timothy J. Whelan

  5. McMaster University, Hamilton, ON, Canada

    Timothy J. Whelan

  6. Wichita NCORP, Wichita, KA, USA

    Bassam I. Mattar

  7. Michiana Hematology-Oncology, P.C., Mishawaka, IN, USA

    Jose A. Bufill

  8. Swedish American Regional Cancer Center, Rockford, IL, USA

    William C. Schultz

  9. Mercy Hospital-Joplin, Joplin, MO, USA

    Irving E. LaFrancis

  10. Mercy Hospital, Coon Rapids, MN, USA

    Gauri G. Nagargoje

  11. West Michigan Cancer Center, Kalamazoo, MI, USA

    Radhakrishna Vemuri

  12. Essentia Health Cancer Center, Duluth, MN, USA

    Daniel A. Nikcevich

  13. Stanford University, Stanford, CA, USA

    George W. Sledge

  14. Northwestern University, Chicago, IL, USA

    David Cella

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  1. Lynne I. Wagner
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  2. Fengmin Zhao
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  4. Judith-Anne W. Chapman
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  14. George W. Sledge
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Correspondence to Lynne I. Wagner.

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Wagner, L.I., Zhao, F., Goss, P.E. et al. Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03). Breast Cancer Res Treat 169, 537–548 (2018). https://doi.org/10.1007/s10549-018-4713-2

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