Patients with metastatic clear cell renal cell carcinoma treated with first-line pazopanib used fewer medical resources than did those receiving sunitinib, according to new details from the phase III COMPARZ trial.
Over the first 6 months of treatment, patients on pazopanib (Votrient) had significantly fewer emergency department visits (cumulative mean, 0.037 vs. 0.067; P = .003) and monthly telephone consultations (mean, 0.279 vs. 0.312; P = .04) than did those receiving first-line sunitinib (Sutent).
Pazopanib patients also had a nonsignificant trend toward fewer days in hospital (mean, 0.402 vs. 0.562; P = .10) and non–study-related medical visits (0.726 vs. 0.779; P = .07), according to the full results of COMPARZ (Comparing the Efficacy, Safety and Tolerability of Pazopanib vs. Sunitinib) published today in the New England Journal of Medicine (2013, Aug. 22;369:722-31).
Dr. Robert Motzer
"Our study showed lower monthly use of medical resources with pazopanib then with sunitinib," wrote lead author Dr. Robert J. Motzer of Memorial Sloan-Kettering Cancer Center in New York. "These endpoints, plus health-related quality of life and the safety profile, assume special importance in comparative-effectiveness research when clinically similar (noninferior) treatments are being considered."
Data presented by Dr. Motzer at the 2012 European Society for Medical Oncology (ESMO) Congress and reported by The Oncology Report show a median progression-free survival of 8.4 months with pazopanib and 9.5 months with sunitinib. Median overall survival also was similar at 28.4 months vs. 29.3 months, respectively.
Where pazopanib appeared to have the advantage was in the secondary endpoints of safety and quality of life. Patients treated with sunitinib had significantly more fatigue (63% vs. 55%), hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%), while those given pazopanib had a higher incidence of elevated alanine aminotransferase (60% vs. 43%), weight loss (15% vs. 6%), and changes in hair color (30% vs. 10%). The authors noted that fatigue, gastrointestinal events, hand-foot syndrome, and liver toxicity have been highlighted as "adverse events of particular concern to patients."
The article expands on the quality-of-life analyses, but the bottom line is that significant differences favored pazopanib over sunitinib for 11 of 14 comparisons. Two other studies, including the PISCES trial also reported at ESMO 2012, support the health-related quality of life results.
"Many oncologists, including the group at MSKCC, have switched their preferred first-line drug from sunitinib to pazopanib," Dr. Motzer said in an interview.
The renal cancer treatment field is crowded, with competitors, however, including sorafenib (Nexavar), bevacizumab (Avastin), temsirolimus (Torisel), and more recently, tivozanib. The hepatotoxicity associated with pazopanib may also deter some clinicians from making the switch.
As for whom sunitinib remains the best option for first-line therapy, Dr. Motzer said, "Sunitinib could be considered the preferred treatment, in my opinion, in patients with underlying liver dysfunction, and in non–clear cell subtypes of kidney cancer."
Officials at GlaxoSmithKline would not comment on the impact of the COMPARZ trial on pazopanib’s market share, noting that they are not marketing against it or using the data in the pazopanib label. Still, U.S. sales figures show pazopanib sales have increased steadily over the last year, doubling from $25 million in the first quarter of 2012 to $51 million for the same period in 2013. Sales in the second quarter of 2013 hit $56 million, according to Bernadette King, director of GSK’s U.S. external communications for oncology.
Earlier this month, GSK filed with the European Medicines Agency for an additional indication for pazopanib as maintenance treatment for advanced stage II-IV ovarian, fallopian tube, or primary peritoneal cancer. Phase III data reported earlier this year show pazopanib maintenance therapy extends progression-free survival by an average of 5.6 months, compared with placebo.
Pazopanib already is recommended by the National Institute for Health and Clinical Excellence (NICE) as first-line treatment for patients in the U.K. with advanced kidney cancer, after GSK officials agreed to a 12.5% discount on the list price and a possible second rebate following the outcome of COMPARZ.
GSK officials are in discussion with U.K. officials on that second "risk-sharing" agreement now that the COMPARZ data are published, but no details are available, Ms. King said.
She noted that the negotiations will not affect the price of pazopanib in the United States, but that GSK offers a range of patient assistance programs for eligible patients in the U.S. The average wholesale acquisition cost for a 30-day supply of pazopanib at the 800-mg dose used in COMPARZ is $7,163. A total of 1,110 patients were randomized to a continuous dose of pazopanib 800 mg once daily or sunitinib 50 mg once daily for 4 weeks, followed by a 2-week drug holiday.