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Proffered Paper – Developmental therapeutics

2651 - Therapeutic drug monitoring of oral anticancer drugs - preliminary results of a prospective study

Date

29 Sep 2019

Session

Proffered Paper – Developmental therapeutics

Topics

Targeted Therapy

Tumour Site

Presenters

Steffie Groenland

Citation

Annals of Oncology (2019) 30 (suppl_5): v159-v193. 10.1093/annonc/mdz244

Authors

S.L. Groenland1, R.A.G. Van Eerden2, S.L. Koolen3, D.J.A.R. Moes4, I.M.E. Desar5, D.J. Touw6, A.L.T. Imholz7, A.K.L. Reyners8, H. Gelderblom9, N.P. van Erp10, R.H.J. Mathijssen11, A.D.R. Huitema12, N. Steeghs1

Author affiliations

  • 1 Medical Oncology & Clinical Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2 Medical Oncology, Erasmus MC Cancer Institute, 3015 CE - Rotterdam/NL
  • 3 Medical Oncology And Hospital Pharmacy, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 4 Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden/NL
  • 5 Medical Oncology, Radboud University Medical Center, Nijmegen/NL
  • 6 Clinical Pharmacy & Pharmacology, University Medical Center Groningen, Groningen/NL
  • 7 Internal Medicine, Deventer Ziekenhuis, 7416 SE - Deventer/NL
  • 8 Medical Oncology, University Medical Center Groningen (UMCG), Groningen/NL
  • 9 Medical Oncology, Leiden University Medical Center, Leiden/NL
  • 10 Pharmacology, Radboud University Medical Center, Nijmegen/NL
  • 11 Medical Oncology, Erasmus MC Cancer Institute, Rotterdam/NL
  • 12 Pharmacy & Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL

Resources

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Abstract 2651

Background

Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK). Even though exposure has been linked to efficacy and toxicity for many of these drugs, they are still dosed using a one-size-fits-all approach. Consequently, individual patients (pts) have a high probability to be either underdosed or overdosed, potentially leading to decreased antitumor efficacy or increased toxicity. Therapeutic drug monitoring (TDM), which is personalised dosing based on measured drug levels, can be used to address these problems and thereby optimize treatment outcomes.

Methods

This prospective clinical study (www.trialregister.nl, NL6695) evaluates the feasibility, tolerability and efficacy of TDM of oral anticancer drugs. In total, 600 pts will be included for 23 different drugs. Pts starting regular treatment with one of these drugs at the approved dose are included. PK sampling is performed 4, 8, and 12 weeks after start of treatment and every 12 weeks thereafter. Drug concentrations are measured and trough concentrations (Cmin) are estimated. In case of Cmin below the predefined target and acceptable toxicity, a PK-guided intervention is recommended. This may include emphasizing compliance, adaptations in concomitant medication (due to drug-drug interactions), concomitant intake with food, splitting intake moments or dose increments.

Results

In total, 274 pts were included (trametinib (n = 43), abiraterone (n = 38), enzalutamide (n = 35), imatinib (n = 33), pazopanib (n = 23), other (n = 102)), of whom 246 pts had available PK data. 83 pts (34%) were underdosed and had ≥ 1 PK samples below the predefined target. In 48 of 246 pts (20%) a PK-guided intervention was performed, which was successful (i.e. target attainment without additional toxicities) in 39 pts (81%). In 35 pts, a PK-guided intervention could not be performed, due to toxicity (17 pts), logistical reasons (13 pts) or lack of physician adherence (5 pts).

Conclusions

This prospective study shows that PK-guided dose optimization of oral anticancer drugs is feasible in clinical practice. A PK-guided intervention was recommended in 20% of the patients and resulted in target attainment without additional toxicities in 81% of these patients.

Clinical trial identification

NL6695; release date: 6 December 2017.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital.

Funding

Unrestricted research grant of Novartis, Pfizer and Roche.

Disclosure

S.L. Koolen: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Roche; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Cristal Therapeutics; Travel / Accommodation / Expenses: Ipsen. D.J.A.R. Moes: Advisory / Consultancy: Sandoz; Advisory / Consultancy, Research grant / Funding (institution): Chiesi Pharmaceuticals. I.M.E. Desar: Research grant / Funding (institution): Novartis; Advisory / Consultancy: Lilly; Advisory / Consultancy: Eisai. D.J. Touw: Advisory / Consultancy: Sanguin; Research grant / Funding (institution): Chiesi Pharmaceuticals. N.P. van Erp: Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Gilead. R.H.J. Mathijssen: Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Honoraria (institution), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (institution): Servier. N. Steeghs: Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): AB Science; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck Sharp & Dohme; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Incyte. All other authors have declared no conflicts of interest.

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