Follow-up data published in the European Association of Urology did not find a significant improvement in overall survival for patients with locally advanced renal cell carcinoma undergoing adjuvant pazopanib treatment.
Adjuvant pazopanib (Votrient) treatment did not positively impact overall survival (OS) rates following resection in patients with locally advanced renal cell carcinoma (RCC), according to data from the phase 3 PROTECT trial (NCT01235962) published in the European Association of Urology.
More, pazopanib as adjuvant treatment did not improve disease-free survival in this group of patients, further confirming the existing literature regarding patients with localized or locally advanced RCC.
“These findings add to the primary outcomes from the PROTECT study [NCT01235962], which indicated that adjuvant pazopanib 600 mg does not prolong DFS following resection of locally advanced RCC,” wrote the investigators who were led by Robert J. Motzer, MD. “Survival analysis showed no difference in OS between the treatment arms. Pazopanib is not recommended as adjuvant therapy following resection of locally advanced RCC.”
When analyzing OS, the research team found no significant differences between the adjuvant pazopanib arm and the placebo arm (HR, 1.0; 95% CI, 0.80-1.26; nominal P >.9).
Overall, when comparing T4 disease with less advanced disease (T1/2 and T3), OS was worse for patients with more advanced disease. For patients with a body mass index (BMI) of 30 kg/m2 or more, OS was better when compared against patients with a lower BMI.
OS rates were significantly better when examining patients who were disease free at the 2-year mark compared with the cohort of patients who relapsed at the 2-year follow-up mark.
In total, deaths were reported for 145 patients in the pazopanib arm and 150 patients in the placebo arm (each, n = 769).
“These analyses indicate that adjuvant pazopanib confers no OS benefit for patients with localized or locally advanced RCC following nephrectomy,” wrote the investigators. “[Adverse event] reporting was consistent with the known safety profile of pazopanib in advanced RCC.”
The randomized, double-blind, placebo-controlled study enrolled 1538 total patients, with a median follow-up duration of 76 months (interquartile range [IQR], 66-84) in the pazopanib arm and 77 months (IQR, 69-85) in the placebo arm.
When examining the 2 patient populations, the most frequent subsequent systemic treatments were VEGFR or mTOR inhibitors, with pazopanib use in 25% (191/769) and placebo in 26% (201/769). Specifically, 65 patients (8.5%) who received pazopanib and 56 (7.3%) who received placebo also received a subsequent immunotherapy regimen.
“Higher pazopanib trough plasma concentrations levels were associated with better DFS but did not increase treatment discontinuations or grade 3/4 adverse events (AEs), with the exception of hypertension,” wrote the investigators. “In this report, we present the final overall survival analysis from the PROTECT trial.”
“Most studies indicate no benefit of adjuvant therapy with VEGFR tyrosine kinase inhibitors in advanced renal cell carcinoma,” wrote the authors. “These analyses indicate that adjuvant pazopanib confers no OS benefit for patients with localized or locally advanced RCC following nephrectomy.”
Motzer RJ, Russo P, Haas N, et al. Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma: Final Overall Survival Analysis of the Phase 3 PROTECT Trial. European Association of Urology. https://doi.org/10.1016/j.eururo.2020.12.029.