Pazopanib Followed by Nivolumab Shows Real-World Benefit in Metastatic RCC

A real-world study in Germany of sequential treatment of pazopanib followed by nivolumab in advanced or metastatic renal cell carcinoma (mRCC) confirms that the regimen has a good benefit-risk profile as well as a favorable overall survival. The authors of the PAZOREAL study, the third interim results of which were presented (abstract 4574) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, point to the need for real-world evidence to monitor introduction of novel therapies into clinical practice and to more generally improve cancer care and outcomes.

“I think it's going to be an interesting study with longer follow-up. This was done in an era when TKIs [tyrosine kinase inhibitors] were the first-line therapy, and nivolumab was shown to extend survival in the second-line, before immunotherapy became first-line,” Tim Gilligan, MD, associate professor and vice chair for education at the Cleveland Clinic Taussig Cancer Institute, told Cancer Network.

The study included 402 patients who were treated between December 2015 and September 2017 with first-line pazopanib (n = 402) followed by second-line nivolumab (n = 127) or everolimus (n = 5). A total of 56 patients were entered into follow-up.

The clinical benefit rate of first-line pazopanib was 58.2% (95% CI, 53.3–62.9%), with a complete response rate of 8.46% and non-progression of disease plus non-complete response in 49.5% of patients. The median overall survival for first-line pazopanib was 29.5 months (95% CI, 23.6 months–N/A), and for first-line pazopanib followed by second-line nivolumab, it was 28.2 months (95% CI, 22.2 months–N/A). Among 81 patients who did not undergo nephrectomy, the median OS was 16.2 months (95% CI, 10.4 months–N/A). The median OS for patients who underwent nephrectomy was not reached at the study cutoff date.

As of November 8, 2018, for all patients, the median time on drug (TD) was 6.6 months (95% CI, 6.0–7.9) for first-line pazopanib compared with 4.1 months (95% CI, 3.2–5.8) for second-line nivolumab. For trial-eligible patients, median TD for first-line pazopanib was 8.1 months (95% CI, 6.6–9.5), and 3.2 months (95% CI, 2.7–6.5) for second-line nivolumab. For trial ineligible patients, the median TD was 6.4 months (95% CI, 4.7–8.6).

Adverse events for pazopanib included diarrhea (35%), nausea (20.3%), and fatigue (17.5%), with grade 3/4 events believed attributable to pazopanib including hypertension (5%), hypertensive crisis (2.3%), and gamma-glutamyl transferase increase (1.8%). Quality of life scored similarly across therapeutic regimens.

Gilligan added that the immediate implications for clinical practice remain a bit unclear. “I’m not even sure when we’re going to use pazopanib now, because the order of therapies has changed. In the second- or third-line, I guess, is the answer,” he said.

In Germany, pazopanib followed by nivolumab is often prescribed as a second-line therapy.