Investigating Real-World Tolerance and Dose Reductions of Oncology Multikinase Inhibitors in a VA Population

Oral multikinase inhibitors (MKIs) are widely used and effective targeted therapies for patients with cancer. These agents can have substantial drug-drug interactions and adverse effects (AEs), which can make them difficult to tolerate. This study sought to evaluate the real-world tolerance of MKIs prescribed by the hematology/oncology clinic at the Veterans Affairs North Texas Health Care System (VANTHCS) to guide clinicians in the selection of starting doses and in setting expectations for the management of dose titrations.

A retrospective chart review of veterans managed by the VANTHCS hematology/oncology clinic with a prescription for axitinib, cabozantinib, lenvatinib, pazopanib, regorafenib, sorafenib, or sunitinib was conducted for patients treated from January 1, 2014, to October 31, 2024. The primary outcome was the evaluation of MKI tolerance through determining the relative dose intensity (RDI) and mean and median time on therapy. Secondary outcomes included rates of AEs and adjustments in doses.

One hundred seventy veterans with 208 MKI prescriptions met the study inclusion criteria. The overall combined mean MKI RDI was 67.5%. Individual mean RDIs were 71.0% for axitinib, 59.6% for cabozantinib, 63.7% for lenvatinib, 82.3% for pazopanib, 61.2% for regorafenib, 49.0% for sorafenib, and 85.5% for sunitinib. The mean and median time on therapy for all MKIs (excluding days of therapy that were held) was 155 and 95 days, respectively. There were 376 AEs. Eighty-one prescriptions (38.9%) started at the indicated dose and 127 prescriptions (61.1%) were initiated at a reduced dose because of baseline concerns. Across both groups, 90 prescriptions (43.3%) required further dose reduction during therapy.

Oncology MKI therapies used at VANTHCS were difficult for veterans to tolerate and ultimately led to suboptimal dosing. Clinicians may use these data to guide decision-making when initiating and managing MKI agents in this population.