A study of patients with metastatic renal cell carcinoma (RCC) compared the effectiveness of standard chemotherapy to a novel tyrosine kinase inhibitor (TKI) with activity against vascular endothelial growth factor in progression-free survival (primary end point) as first-line treatment. Tumor response was significant in both groups at final follow-up (p

Question

A study of patients with metastatic renal cell carcinoma (RCC) compared the effectiveness of standard chemotherapy to a novel tyrosine kinase inhibitor (TKI) with activity against vascular endothelial growth factor in progression-free survival (primary end point) as first-line treatment.  Tumor response was significant in both groups at final follow-up (p < 0.05).  The Kaplan-Meier survival curve for overall survival is shown below.  Treatment-related adverse events such as diarrhea, nausea, vomiting, hypertension, hand-foot syndrome, asthenia, leukopenia, neutropenia, thrombocytopenia, lymphopenia, and increased lipase and uric acid occurred more frequently in the TKI group than in the standard chemotherapy group (p < 0.05).  Based on the findings of this study, which of the following conclusions is justified?

Quizplus · Accepted Answer

Explanation: The Kaplan-Meier (KM) statistical method is used in survival analysis to analyze time-to-event data, which refers to the time from entry into a study until an event of interest (eg, disease progression, death) occurs. Because such events may occur at different points in time for different study participants, the KM method compares the rate at which these events occur during the entire study period rather than at the end of the study only. As the study progresses, events of interest (eg, death) occur and the proportion of subjects at risk for such events decreases (eg, overall survival decreases), causing a downward dip in the curve. The KM method may be used to compare hazard ratios (HRs) between 2 groups (eg, comparing 2 different treatments). HR is the hazard rate of an event (eg, disease progression) in the intervention group (eg, tyrosine kinase inhibitor [TKI]) divided by the hazard rate of the same event in the comparison group (eg, standard chemotherapy): HR = (hazard rate in the intervention group) / (hazard rate in the comparison group) The hazard rate represents the probability that an individual experiences an event of interest at a particular point after the intervention assuming this individual has survived to that point without experiencing any such event. A confidence interval (CI) that excludes the null value (ie, HR = 1.0) is statistically significant. This study reported significant tumor response in both groups at final follow-up (p < 0.05), with no difference in overall survival between the groups because the CI crosses 1.0 (HR = 0.821; 95% CI: 0.673-1.001) (Choice D). Results also show that treatment-related adverse events occurred more frequently in the TKI group than in the standard chemotherapy group (p < 0.05). Although both treatments led to satisfactory outcomes, TKI therapy resulted in more frequent adverse events compared with standard chemotherapy. Therefore, standard chemotherapy should be recommended because it may be more manageable for patients (Choices A and B). Educational objective: The Kaplan-Meier survival curve is a commonly used graphic representation of the probabilities that participants survive a study without experiencing an event of interest. The hazard rate between 2 groups can be compared; they are statistically different only if the confidence interval excludes the null value.

A Study of Patients with Metastatic Renal Cell Carcinoma (RCC)