VIENNA – The first head-to-head comparison of pazopanib and sunitinib is likely to reshape first-line treatment for renal cell carcinoma, long dominated by sunitinib.
The phase III COMPARZ trial shows similar potency for the two angiogenesis inhibitors, but pazopanib (Votrient) had a better tolerance and safety profile, Dr. Robert Motzer reported at the European Society for Medical Oncology (ESMO) Congress.
As previously observed in indirect comparisons, hand-foot syndrome, fatigue, and mucositis were more common with sunitinib (Sutent), while pazopanib had a higher incidence of liver abnormalities. The adverse events associated with sunitinib are the ones that really affect patients’ day-to-day living, remarked Dr. Motzer of Memorial Sloan–Kettering Cancer Center in New York.
Patrice Wendling/IMNG Medical Media
Dr. Robert Motzer
This was expressed in patient-reported outcomes on four quality of life instruments, which favored pazopanib in all but 1 of 14 domains – the exception was the emotional domain of the FACT Kidney Symptom Index (FKSI-19), but this was not statistically significant.
"This trial tips the scale for the preferred treatment, in my opinion, for most patients with kidney cancer from sunitinib, which has been the reference standard, to pazopanib," he said during a press briefing.
COMPARZ (Comparing the Efficacy, Safety and Tolerability of Pazopanib vs. Sunitinib) randomized 1,110 treatment-naive patients with locally advanced or metastatic clear cell renal cell carcinoma (RCC) to pazopanib 800 mg administered daily on a continuous dosing schedule or sunitinib 50 mg given daily in a 6-week cycle of 4 weeks on, 2 weeks off.
Disease assessments were at weeks 6, 12, 18, 24, and then every 12 weeks. Patient-reported outcomes were measured at day 28 of every cycle.
The primary end point of median progression-free survival was 8.4 months for pazopanib and 9.5 months for sunitinib by independent central review (hazard ratio, 1.047), and 10.5 months vs. 10.2 months by the investigators (HR, 0.998). The upper bound of the 95% confidence interval for the hazard ratio was below 1.25, demonstrating the noninferiority of pazopanib to sunitinib, Dr. Motzer said.
The overall response rate (complete plus partial responses) was 31% for pazopanib and 25% for sunitinib (P = .03).
Median overall survival was 28.4 months vs. 29.3 months (HR, 0.908; P = .27), according to an interim analysis. The final overall survival data is anticipated in 2013, Dr. Motzer said.
Treatment-emergent hypertension, diarrhea, and nausea of any grade occurred equally in both arms. Patients given pazopanib had more hair-color changes (30% vs. 10%) and increased alanine transaminase (ALT) levels (31% vs. 18%), reflecting known increased liver toxicity, he said. In contrast, those given sunitinib experienced more fatigue (63% vs. 55%), hand-foot problems (50% vs. 29%), taste alterations (36% vs. 26%), and thrombocytopenia (34% vs. 10%).
Serious adverse events occurring in 3% or more of patients were increased ALT and increased aspartate aminotransferase (AST) in the pazopanib arm, and pyrexia and thrombocytopenia in the sunitinib arm. Fatal adverse events were reported in 2% and 3%, respectively.