Introduction:
Cabozantinib is a tyrosine kinase inhibitor approved for treatment of renal cell carcinoma. Cabozantinib is started at 60 mg daily, ingested in fasted state. Dose reductions are needed in 67% of patients due to toxicity, without reduce in treatment costs due to a flat pricing model. Alternative dosing strategies are warranted to improve the toxicity profile and reduce treatment costs. Previous studies have shown cabozantinib AUC increased 57% after taking cabozantinib with a high fat meal. The increase in bioavailability when taken with a light breakfast is still unknown. In this study we aim to determine the increase of cabozantinib AUC when taken with a light breakfast.

Methods:
A multicentre, open label, randomized cross-over pharmacokinetic evaluation study was performed. In the standard regimen, patients took cabozantinib in fasted condition. In the experimental regimen, patients took cabozantinib with a light breakfast. After 4 weeks on the allocated regimen, pharmacokinetic samples were obtained at t=0,1,2,3,4,6,8 and 24 hours after dose intake and patients thereafter switched to the other regimen. Patients were monitored for (S)AEs.

Results:
Twelve patients completed study procedures. AUC0-24 for taking cabozantinib in fasted and fed state were 11530 ug/L and 12530 ug/L respectively (CV 10.1%). Mean difference was 8.3% (ratio 90% CI 100.9 – 117.12). No differences in adverse events were established.

Discussion and conclusion:
This study demonstrates taking cabozantinib with a commonly used breakfast leads to a slight increase in exposure, but with no apparent impact on adverse events. These results support to ingest cabozantinib with food without clinically relevant influence on exposure.

This presentation showcases research underpinned by data transparency frameworks that enabled negotiation of access to patient-level data from over 100 industry-sponsored oncology trials. These rich datasets have facilitated investigations into how gastrointestinal-modifying concomitant medicines influence survival and adverse event outcomes in cancer.
Key findings from Associate Professor Ashley Hopkins’ work demonstrate that proton pump inhibitor (PPI) use is associated with poorer survival benefit from immunotherapies, such as atezolizumab, in non-small cell lung cancer. Large-scale prognostic analyses further reveal that PPI exposure correlates with reduced overall survival and worsened toxicity in colorectal and breast cancer cohorts. Methodological approaches include multivariable Cox regression and pooled post hoc trial evaluations, illustrating how systematic analyses of participant-level data can uncover clinically meaningful drug interactions.
These results underscore the urgent need to advocate for and expand transparent access to trial data. Findings highlight that GI modulating drugs can alter the gut microbiota and gastric pH, affecting drug absorption, pharmacokinetics, and pharmacodynamics—factors of growing importance as oncology shifts toward orally administered targeted therapies.

During the past decades, small-molecule kinase inhibitors have proven to be valuable in the treatment of solid and haematological tumours. However, because of their oral administration, the intrapatient and interpatient exposure to small-molecule kinase inhibitors (SMKIs) is highly variable and is affected by many factors, such as concomitant use of food and herbs. Food–drug interactions are capable of altering the systemic bioavailability and pharmacokinetics of these drugs. The most important mechanisms underlying food–drug interactions are gastrointestinal drug absorption and hepatic metabolism through cytochrome P450 isoenzymes. As food–drug interactions can lead to therapy failure or severe toxicity, knowledge of these interactions is essential.
Therefore, general principles involving food–drug interactions and herb–drug interactions for SMKIs will be presented. For illustration, the design and results of specific studies will be discussed more extensively. Also, US Food and Drug Administration (FDA) and European Medicines Agency (EMA) recommendations concerning food-drug interactions are considered. Based on current available information, clear recommendations for their management will be provided, and suggestions for performing food-drug studies during drug development phases and thereafter.

Abiraterone acetate is a cornerstone in the management of metastatic castration-resistant prostate cancer (mCRPC). Given its food effect on absorption, we compared outcomes between a low-dose (250 mg daily- Arm A) and standard-dose (1000 mg daily – Arm B) abiraterone regimen. The low-dose abiraterone was administered with a low-fat meal, whereas the standard dose was administered in fasting state as per standard recommendations. The objective of the study was to assess whether lower dosing could maintain efficacy and safety while improving cost-effectiveness. In this study, overall survival (OS) and median prostate-specific antigen progression-free survival (PSA-PFS) were comparable between the two arms [PSA-PFA = 5.7 vs 3.8 months, HR=0.95; OS = 18.1 vs 15.1 months, HR=0.99]. Similarly, the incidence of grade ≥3 adverse events did not differ significantly [36.6% vs 31.6%, p=0.51]. Pharmacokinetic (PK) analysis showed that both area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) were lower in the low-dose arm compared to the standard-dose arm [AUC = 28.7 vs 226 ng/ml*h], indicating reduced systemic exposure. Importantly, the anticipated improvement in bioavailability with a low-fat diet was not observed in the low-dose group. Despite lower PK exposure, clinical outcomes and toxicity remained similar between low-dose and standard-dose treatments. These findings suggest that administering low-dose abiraterone with a low-fat meal does not enhance bioavailability but achieves comparable survival and safety outcomes to the standard regimen. This approach could represent a meaningful strategy for substantial cost savings without compromising patient care.