Cancer patients tend to prefer oral instead of parenteral chemotherapy. To date, there is little evidence on the medication adherence in cancer patients. We investigated medication adherence to tyrosine kinase inhibitors in patients suffering from non-small cell lung cancer.
Methods
Tyrosine kinase inhibitor adherence was measured electronically by MEMS® (medication event monitoring system) over at least six months. Adherence rates were calculated in terms of Dosing Compliance, Timing Compliance, Taking Compliance, and Drug Holidays. Patients were dichotomized as adherent when Dosing Compliance and Timing Compliance were ≥80%, Taking Compliance ranged between 90 and 110%, and <1 Drug Holiday was registered. Quality of life was assessed by two questionnaires (EORTC QLQ-C30 version 3.0, EORTC QLQ-LC13) at three time points. Adverse drug events were reported via patient diaries.
Results
Out of 32 patients enrolled, data from 23 patients were evaluable. Median Dosing Compliance, Taking Compliance, and Timing Compliance adherence rates of tyrosine kinase inhibitor intake amounted to 100%, 98%, and 99%, respectively; Drug Holidays were observed in three patients. Four patients were dichotomized as non-adherent. Three of them had a twice-daily tyrosine kinase inhibitor regimen. Median quality of life scores amounted to 67 (max. 100) and remained unchanged over the study period. Fatigue and rash were the most frequently reported adverse drug events.
Conclusion
Medication adherence of non-small cell lung cancer patients treated with tyrosine kinase inhibitors was extraordinarily high and is likely to support the effectiveness of tyrosine kinase inhibitor treatment and a good quality of life over a long period of time. Adherence facilitating information and education is especially relevant for patients taking tyrosine kinase inhibitors in a twice-daily regimen.
BrayFFerlayJSoerjomataramI, et al.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2018;
68: 394–424.
2.
American Cancer Society. Cancer facts & figures 2019.
Atlanta:
American Cancer Society, 2019.
3.
PlanchardDPopatSKerrK, et al.
Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol2018;
29: iv192–iv237.
4.
LiuGFranssenEFitchMI, et al.
Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol1997;
15: 110–115.
5.
EekDKroheMMazarI, et al.
Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: a review of the literature. Patient Prefer Adherence2016;
10: 1609–1621.
6.
World Health Organization.Adherence to long term therapies: evidence for action.
Geneva:
WHO, 2003.
RuddyKMayerEPartridgeA.Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin2009;
59: 56–66.
9.
Regnier DenoisVPoirsonJNourissatA, et al.
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: 520–527.
10.
CutlerRLFernandez-LlimosFFrommerM, et al.
Economic impact of medication non-adherence by disease groups: a systematic review. BMJ Open2018;
8: e016982.
11.
GreerJAAmoyalNNisotelL, et al.
A systematic review of adherence to oral antineoplastic therapies. Oncologist2016;
21: 354–376.
12.
BarilletMPrevostVJolyF, et al.
Oral antineoplastic agents: how do we care about adherence?Br J Clin Pharmacol2015;
80: 1289–1302.
13.
BoucherJLuccaJHooperC, et al.
A structured nursing intervention to address oral chemotherapy adherence in patients with non-small cell lung cancer. Oncol Nurs Forum2015;
42: 383–389.
14.
GebbiaVBellaviaMBannaGL, et al.
Treatment monitoring program for implementation of adherence to second-line erlotinib for advanced non-small-cell lung cancer. Clin Lung Cancer2013;
14: 390–398.
15.
Engel-Nitz NicoleMNm Satram-HoangSCaoF, et al.
Lung cancer: copayments and behavior following erlotinib formulary tier change. Am J Pharm Benef2012;
4: SP6–SP16.
16.
TimmersLBoonsCMoes-Ten HoveJ, et al.
Adherence, exposure and patients' experiences with the use of erlotinib in non-small cell lung cancer. J Cancer Res Clin Oncol2015;
141: 1481–1491.
17.
HessLMLouderAWinfreeK, et al.
Factors associated with adherence to and treatment duration of erlotinib among patients with non-small cell lung cancer. JMCP2017;
23: 643–652.
18.
TorrecillasSPerrotEGérinièreL, et al.
Croyances des patients envers les thérapies ciblées orales et leur influence sur l'observance dans le cancer broncho-pulmonaire une étude pilote prospective. Rev Pneumol Clin2016;
72: 25–34.
19.
DammKRoeskeNJacobC.Health-related quality of life questionnaires in lung cancer trials: a systematic literature review. Health Econ Rev2013;
3: 15.
20.
BaschEIasonosAMcDonoughT, et al.
Patient versus clinician symptom reporting using the National Cancer Institute common terminology criteria for adverse events: results of a questionnaire-based study. Lancet Oncol2006;
7: 903–909.
21.
VerbruggheMVerhaegheSLauwaertK, et al.
Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: a systematic review. Cancer Treat Rev2013;
39: 610–621.
22.
VrijensBGoetghebeurE.Comparing compliance patterns between randomized treatments. Control Clin Trials1997;
18: 187–203.
23.
AaronsonNKAhmedzaiSBergmanB, et al.
The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst1993;
85: 365–376.
24.
BergmanBAaronsonNKAhmedzaiS, et al.
The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC study group on quality of life. Eur J Cancer1994;
30: 635–642.
25.
FayersPMAaronson NKBjordalK, et al. The EORTC QLQ-C30 scoring manual. 3rd ed.Brussels:
European Organisation for Research and Treatment of Cancer, 2001.
26.
OsobaDRodriguesGMylesJ, et al.
Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol1998;
16: 139–144.
27.
DenhaerynckKSchäfer-KellerPYoungJ, et al.
Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients. BMC Med Res Methodol2008;
8: 5.
28.
TimmersLBoonsCKropffF, et al.
Adherence and patients' experiences with the use of oral anticancer agents. Acta Oncol2014;
53: 259–267.
29.
PartridgeAHAvornJWangPS, et al.
Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst2002;
94: 652–661.
30.
DeschampsAEvan WijngaerdenEDenhaerynckK, et al.
Use of electronic monitoring induces a 40-day intervention effect in HIV patients. J Acquir Immune Defic Syndr2006;
43: 247–248.
31.
GastAMathesT.Medication adherence influencing factors – an (updated) overview of systematic reviews. Syst Rev2019;
8: 112.
32.
EberlinMOttoGKrämerI.Increased medication compliance of liver transplant patients switched from a twice-daily to a once-daily tacrolimus-based immunosuppressive regimen. Transplant Proc2013;
45: 2314–2320.
33.
KollerMHjermstadMJTomaszewskiKA, et al.
An international study to revise the EORTC questionnaire for assessing quality of life in lung cancer patients. Ann Oncol2017;
28: 2874–2881.
34.
HungH-YWuL-MChenK-P.Determinants of quality of life in lung cancer patients. J Nurs Scholarsh2018;
50: 257–264.
35.
LarssonMLjungLJohanssonBBK.Health-related quality of life in advanced non-small cell lung cancer: correlates and comparisons to normative data. Eur J Cancer Care (Engl)2012;
21: 642–649.
36.
BezjakATuDSeymourL, et al.
Symptom improvement in lung cancer patients treated with erlotinib: quality of life analysis of the National Cancer Institute of Canada clinical trials group study BR.21. JCO2006;
24: 3831–3837.
37.
BouazzaYBChiairiIEl KharbouchiO, et al.
Patient-reported outcome measures (PROMs) in the management of lung cancer: a systematic review. Lung Cancer2017;
113: 140–151.
38.
BoonsCTimmersLvan SchoorNM, et al.
Patient satisfaction with information on oral anticancer agent use. Cancer Med2018;
7: 219–228.
39.
RieseCWeißBBorgesU, et al.
Effectiveness of a standardized patient education program on therapy-related side effects and unplanned therapy interruptions in oral cancer therapy: a cluster-randomized controlled trial. Support Care Cancer2017;
25: 3475–3483.
40.
HorneRHankinsMJenkinsR.The Satisfaction with Information about Medicines Scale (SIMS): a new measurement tool for audit and research. Qual Health Care2001;
10: 135–140.
41.
ArrarasJIGreimelESezerO, et al.
An international validation study of the EORTC QLQ-INFO25 questionnaire: an instrument to assess the information given to cancer patients. Eur J Cancer2010;
46: 2726–2738.
42.
MoriskyDEGreenLWLevineDM.Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care1986;
24: 67–74.
43.
MislangARWildesTMKanesvaranR, et al.
Adherence to oral cancer therapy in older adults: the International Society of Geriatric Oncology (SIOG) taskforce recommendations. Cancer Treat Rev2017;
575: 8–66.
