No Benefit With Post-Nephrectomy Pazopanib in Local RCC

Article

Treatment with pazopanib 600 mg had no benefit over placebo for patients who had undergone nephrectomy for localized or locally advanced renal cell carcinoma.

Treatment with pazopanib 600 mg had no benefit over placebo for patients who had undergone nephrectomy for localized or locally advanced renal cell carcinoma (RCC), according to results of the phase III PROTECT trial published in the Journal of Clinical Oncology.

However, patients in the intent-to-treat (ITT) 800-mg pazopanib group had a decrease in relative risk for recurrence or death, but this group represented only about one-third of the study population.

“The difference in treatment effect between the two groups might be explained by the better performance of the placebo arm in the ITT600mg group compared with that in the ITT800mg group, although this observation is not based on a randomized comparison,” wrote Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, and colleagues.

Antiangiogenics like pazopanib are a standard part of treatment for patient with advanced RCC. This trial was designed to test pazopanib in patients with locally advanced disease at high risk for relapse after nephrectomy. The study included 1,538 patients with resected disease who were randomly assigned to pazopanib or placebo. The starting dose for pazopanib was 800 mg and 403 patients received this dose. However, to address toxicity attrition the starting dose was decreased to 600 mg and the primary endpoint was adjusted to disease-free survival for pazopanib 600 mg.

The trial failed to meet its primary endpoint. There was no improvement in disease-free survival for patients assigned pazopanib 600 mg compared with placebo. Looking at the smaller group of patients assigned to 800-mg pazopanib, there was a significant improvement in disease-free survival (HR, 0.69; 95% CI, 0.51–0.94) compared with placebo. With 1 year of additional follow-up, patients assigned to 800 mg had a 33.7% decreased relative risk for recurrence or death. The median disease-free survival was 54 months for placebo and not yet reached for pazopanib 800 mg.

“Although the intent of modifying the protocol dose of pazopanib from 800 to 600 mg was to reduce the rate of discontinuation and improve the safety profile, the proportions of patients in both cohorts had similar discontinuation rates and safety,” the researchers wrote. “The rate of pazopanib discontinuation because of adverse events in PROTECT (35% to 39%) was higher compared with that observed in two large phase III studies in advanced or metastatic RCC (14% and 24%, respectively).”

Patients in both the 600 mg and 800 mg groups had a similar duration of exposure, with about one-half of patients completing 12 months of treatment in both groups. Increased ALT and AST were common adverse events that led to treatment discontinuation in the pazopanib 600 mg and 800 mg groups. 

Newsletter

Stay up to date on recent advances in the multidisciplinary approach to cancer.

Recent Videos
A phase 0 trial is seeking to assess the feasibility of aiding anti-cancer cells with cytokines to restore their function.
Although pembrolizumab addressed a long-standing need in adjuvant kidney cancer treatment, combinations with the agent may further bolster efficacy.
“The trial will be successful, or [we’ll] declare it a success if we see at least 3 of 24 responses overall,” stated Ravi, MD, BChir, MRCP, on the phase 2 LASER trial in RCC.
Success with the 177Lu-PSMA-617 radioligand therapy would be transformative for the clear cell renal cell carcinoma treatment landscape.
An ongoing phase 1 trial seeks to prove XmAb819 as an effective treatment and ENPP3 as a plausible target in patients with relapsed or refractory RCC.
“The therapy is designed to prevent both CAR T-cell inactivation and to restore the anti-tumor immunity of the white blood cells that have gotten through the tumor,” said Marasco, MD, PhD.
Ongoing studies aim to combine base immunotherapy regimens with novel agents to potentially improve outcomes among patients with kidney cancer.
Investigators have found a way to reduce liver and biliary toxicity when targeting the molecule CAIX in patients with clear cell renal cell carcinoma.
Neoantigen-targeting vaccines resulted in an absence of recurrence in 9 patients with high-risk kidney cancer, according to David A. Braun, MD, PhD.
The Kidney Cancer Research Consortium may allow collaborators to form more mechanistic and scientifically driven efforts in the field.
Related Content