Optimizing Oral Targeted Anticancer Therapies Study for Patients With Solid Cancer: Protocol for a Randomized Controlled Medication Adherence Program Along With Systematic Collection and Modeling of Pharmacokinetic and Pharmacodynamic Data

Carole Bandiera, Evelina Cardoso, Isabella Locatelli, Antonia Digklia, Khalil Zaman, Antonella Diciolla, Valérie Cristina, Athina Stravodimou, Aedo Lopez Veronica, Ana Dolcan, Apostolos Sarivalasis, Aikaterini Liapi, Hasna Bouchaab, Angela Orcurto, Jennifer Dotta-Celio, Solange Peters, Laurent Decosterd, Nicolas Widmer, Dorothea Wagner, Chantal Csajka, Marie Paule Schneider, Carole Bandiera, Evelina Cardoso, Isabella Locatelli, Antonia Digklia, Khalil Zaman, Antonella Diciolla, Valérie Cristina, Athina Stravodimou, Aedo Lopez Veronica, Ana Dolcan, Apostolos Sarivalasis, Aikaterini Liapi, Hasna Bouchaab, Angela Orcurto, Jennifer Dotta-Celio, Solange Peters, Laurent Decosterd, Nicolas Widmer, Dorothea Wagner, Chantal Csajka, Marie Paule Schneider

Abstract

Background: The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response.

Objective: The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations.

Methods: The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits.

Results: The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022.

Conclusions: The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients' needs and to consider their concerns about their PKI self-management, considering the patient as an active partner.

Trial registration: ClinicalTrials.gov NCT04484064; https://ichgcp.net/clinical-trials-registry/NCT04484064.

International registered report identifier (irrid): DERR1-10.2196/30090.

Keywords: NONMEM; adherence electronic measure; interprofessional program; medication adherence; motivational interviewing; neoplasms; oral anticancer therapies; pharmacodynamics; pharmacokinetics.

Conflict of interest statement

Conflicts of Interest: None declared.

©Carole Bandiera, Evelina Cardoso, Isabella Locatelli, Antonia Digklia, Khalil Zaman, Antonella Diciolla, Valérie Cristina, Athina Stravodimou, Aedo Lopez Veronica, Ana Dolcan, Apostolos Sarivalasis, Aikaterini Liapi, Hasna Bouchaab, Angela Orcurto, Jennifer Dotta-Celio, Solange Peters, Laurent Decosterd, Nicolas Widmer, Dorothea Wagner, Chantal Csajka, Marie Paule Schneider. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 29.06.2021.

Figures

Figure 1
Figure 1
Design of the optimizing oral targeted anticancer therapies study. BMQ: Belief about Medicines Questionnaire; EORTC-QLQ: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; SatMed: Treatment Satisfaction with Medicines Questionnaire.

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