FIGON DMD

Joanneke Overbeek

RadboudUMC

Joanneke Overbeek is a pharmacist and PhD-candidate at the Department of Pharmacy of the Radboudumc in Nijmegen. In 2021, she started her doctoral research under the supervision of prof. Nielka van Erp, prof. Haiko Bloemendal, dr. Nelleke Ottevanger and dr. Rob ter Heine.

Her research focusses on alternative dosing regimens of oraltargeted anticancer drugs. She investigates novel dosing regimens in clinical trials and with pharmacometric models with the ultimate goal to improve the tolerability and affordability of registered anticancer drugs.

Presentation: Off-label, but on-target: alternative dosing regimens for anticancer drugs

Abstract: The past decades, new anticancer treatments have drastically improved survival of cancer patients. The novel therapies are highly effective, but several challenges in the use of these drugs remain. Many anticancer drugs are registered near the maximum tolerated dose, even if a lower dose could have similar efficacy. Furthermore, patients are exposed to side effects for a prolonged period since novel anticancer drugs are often continuously used until disease progression. Therefore, even mild side effects will have a substantial impact on a patient’s quality of life. Finally, the rapidly rising costs of anticancer drugs raise concerns about the affordability and accessibility of new and expensive therapies in the future. Alternative dosing regimens provide a solution for these challenges. Two promising alternative dosing regimens are investigated.

First, a reduced dose of enzalutamide was studied to improve tolerability. This alternative dosing regimen was evaluated in a randomized trial in frail patients with prostate cancer. Patients treated with the standard dose of enzalutamide experienced more fatigue and cognitive side effects over time. Patients treated with the reduced dose remained stable over time. Therefore, the reduced dose can result in less fatigue and cognitive side effects compared to the standard dose.

Second, pharmacokinetic boosting of olaparib with the strong CYP3A-inhibitor cobicistat is studied to improve affordability and tolerability. A pharmacokinetic cross-over study evaluated olaparib exposure in patients with solid tumors, who were treated with olaparib monotherapy and boosted therapy. Pharmacokinetic boosting increased olaparib exposure, despite a threefold dose reduction of olaparib. Moreover, variability in intrinsic clearance of olaparib was lower with the boosted therapy. A non-inferiority trial is ongoing to establish the long-term efficacy and tolerability of boosted olaparib.

These studies show how alternative dosing regimens can be used to optimize anticancer therapies. Both dose reductions and pharmacokinetic boosting are promising strategies to increase tolerability and affordability.