Effect of Pazopanib on Survival After Metastasectomy in Metastatic RCC

Among metastatic renal cell carcinoma (mRCC) patients with no evidence of disease (NED) after metastasectomy, treatment with pazopanib did not confer any survival benefit. In fact, there was a survival trend in favor of the placebo group. The study follows on previous failures to demonstrate benefit from a systemic therapy in this population, which is at a high risk for recurrence.

Metastasectomy in mRCC has long been a mainstay of practice, but recurrence is common, even in patients with no evidence of disease. Some systemic therapies have shown benefit in patients with measurable metastatic burden following surgery, but the biological impact of these drugs may be different in the two populations, and it’s unclear whether they could reduce recurrence in the NED population.

The trial data (abstract 4502) was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago. The findings are in line with previous studies showing no benefit of pazopanib after nephrectomy (PROTECT) and the use of sorafenib after metastasectomy (RESORT).

Pazopanib inhibits vascular endothelial growth factor and other kinases, and has been shown to improve progression-free survival; it has also been approved by the US Food and Drug Administration for the treatment of mRCC. The researchers randomized 129 patients (performance status, 0 to 1) to receive daily pazopanib or placebo for 52 weeks. Most patients had metachronous disease rather than synchronous disease. Clinicians assessed patients for toxicity and patient-reported outcomes at 4-week intervals, while restaging scans were performed every 12 weeks.

An analysis found a failure to meet the primary endpoint: disease-free survival was in favor of pazopanib, but was not statistically significant (hazard ratio [HR], 0.85; 95% CI, 0.55–1.31). The median disease-free survival was 14.2 months for placebo vs 17.3 months for pazopanib.

Patients with a disease-free interval of greater than 1 year prior to surgery had improved disease free survival (DFS) compared with those with a disease-free survival of 1 year or less (HR, 0.55; log rank P = .01). There was no difference in DFS between patients with a single site vs more than one resected site.

Overall survival favored placebo (OS, 2.65; P = .05). Most deaths occurred after study treatment.

One important limitation of the study is that it used pazopanib, which is no longer a front-line therapy. Leonard Appleman, MD, PhD, who presented the study, noted that newer trials are ongoing to look at the effects of nivolumab (PROSPER-RCC), pazopanib (metastasectomy within 1 year; KEYNOTE 564), and atezolizumab (IMmotion010). Appleman is an assistant professor of medicine at the University of Pittsburgh.

Appleman also discussed the challenge of achieving sufficient statistical power, and found sympathy from Robert Dreicer, MD, deputy director of the University of Virginia Cancer Center, who told Cancer Network that the new studies may take a while to complete due to the difficulty in finding sufficient patients to enroll. “It’s not the easiest subset to find,” he said.