Efficacy and Safety of Pazopanib and Sunitinib in Patients with Metastatic Renal-cell Carcinoma as First-line Treatment

4 Apr, 22

Introduction

The tyrosine kinase inhibitors, pazopanib and sunitinib are first-line treatment options for treatment of clear-cell, metastatic renal-cell carcinoma.

Aim

This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy in patients with metastatic renal-cell carcinoma as first-line treatment

Patient Profile

Patients 18 years of age or older
Having advanced or metastatic renal-cell carcinoma with a clear-cell histologic component and had not received systemic treatment previously

Methods

Randomized, open-label, phase 3 trial

Study Drugs

Pazopanib was administered orally at a once-daily dose of 800 mg, with continuous dosing.
Sunitinib was administered orally in 6-week cycles at a once-daily dose of 50 mg for 4 weeks, followed by 2 weeks without treatment

Endpoint

The primary end point was progression- free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib
Secondary end points included overall survival, safety, and quality of life

Results

Efficacy: Progression Free Survival (PFS)

Pazopanib demonstrated noninferiority to sunitinib with respect to PFS (hazard ratio for progression of disease or death from any cause, 1.05
- Disease-progression events occurred in 336 of 557 patients (60%) in the pazopanib group and in 323 of 553 (58%) in the sunitinib group

Figure 1: PFS with pazopanib and sunitinib

Efficacy: Tumor Response

Objective response rates were higher with pazopanib than with sunitinib
Investigator-assessed objective response rates were similar between the two groups

Table 1: Tumour Response with pazopanib vs sunitinib

Response	Pazopanib	Sunitinib	p-value
Partial	31%	24%
Complete	1 patient	3 patients
Objective	31%	25%	p=0.03
Investigator assessed objective response	31%	29%	0.12

Overall Survival

Overall survival was similar in the two groups (hazard ratio for death with pazopanib vs. sunitinib, 0.91; p = 0.28 by a stratified log rank test)

Figure 2: Median overall survival in pazopanib group and sunitinib group

Safety

Pazopanib and sunitinib groups had similar rates of dose reduction and drug discontinuation because of adverse events

Elevations in liver-function tests, weight loss, and changes in hair color were more common with pazopanib than with sunitinib.
- pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib)
Most adverse events, particularly those associated with discomfort, such as fatigue, the hand– foot syndrome, and mouth sores, occurred more frequently with sunitinib than with pazopanib.
- incidence of fatigue (sunitinib 63% vs. pazopanib 55%),
- the hand–foot syndrome (sunitinib 50% vs. pazopanib 29%)
- thrombocytopenia (sunitinib 78% vs. pazopanib 41%)
The incidence of myocardial infarction or ischemia was similar in the pazopanib and sunitinib groups (2% and 4%, respectively)
Analyses of health-related quality of life showed that patients who received pazopanib reported less fatigue, fewer side effects such as soreness of the hand or foot and soreness of the mouth or throat, and better satisfaction with treatment than did those who received sunitinib
- The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favoured pazopanib (p<0.05 for all 11 comparisons)

Conclusion

The study showed noninferiority of progression-free survival with pazopanib versus sunitinib
The similar rates of overall survival in the two groups and the higher objective response rates observed with pazopanib versus sunitinib are consistent with noninferiority in overall efficacy
Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favour pazopanib

Reference

N Engl J Med 2013; 369:722-31.