Impact of adverse events, treatment modifications, and dose intensity on survival among patients with advanced renal cell carcinoma treated with first‐line sunitinib: a medical chart review across ten centers in five European countries

Abstract

Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity.

Predictive biomarker candidates to delineate efficacy of antiangiogenic treatment in renal cell carcinoma

“…This situation can lead to premature treatment discontinuations in cases where a pseudoprogression is detected and also biasing studies focused on biomarkers since that case will be erroneously classified, with a deleterious impact on survival [12,78].…”

“…Such a profile could, for instance, make that patients with a predicted sensitivity to one drug were preserved from unjustified dose reductions that have been correlated with a shorter survival [12].…”

Angiogenic, inflammatory and immunologic markers in predicting response to sunitinib in metastatic renal cell carcinoma

“…Previous studies have demonstrated that on‐treatment hypertension, thrombocytopenia and relative dose intensity are useful biomarkers to predict sunitinib efficacy . Indeed, in our cohort, on‐treatment hypertension and longer sunitinib treatment period predicted better survival.…”

Efficacy and safety of axitinib for metastatic renal cell carcinoma in patients on hemodialysis for end‐stage renal disease: Case series of eight patients

“…This approach can allow continuous administration and prevention of DLTs. For other VEGFR inhibitors, such as sorafenib or sunitinib, sufficient dose intensity and continuous treatment are required to maintain efficacy . Taken together, these findings show that under careful management, axitinib can exhibit feasible efficacy and tolerable safety in patients on hemodialysis.…”