FDA Approves New Pazopanib Formulation for RCC and Soft Tissue Sarcoma
核心洞察
The FDA has approved a new 200 mg formulation of pazopanib tablets for advanced renal cell carcinoma (搜索) (RCC) and soft tissue sarcoma (搜索) (STS).
This approval is based on demonstrated bioequivalence and therapeutic equivalence to the reference pazopanib (Votrient).
Pazopanib was previously approved for advanced RCC in 2009 and advanced STS (post-chemotherapy) in 2012.
The FDA has granted approval to a new formulation of pazopanib tablets, offering a 200 mg dosage for the treatment of advanced renal cell carcinoma (搜索) (RCC) and advanced soft tissue sarcoma (搜索) (STS) following prior chemotherapy. This announcement comes from Aurobindo Pharma Limited, the developer of the new formulation.
Eugia Pharma Specialties Limited (搜索), a subsidiary of Aurobindo Pharma, will be responsible for marketing and manufacturing the 200 mg pazopanib tablets. The approval is based on evidence of bioequivalence and therapeutic equivalence to the original pazopanib formulation (Votrient).
The reference pazopanib received its initial FDA approval for advanced RCC in October 2009 and subsequently for advanced STS, specifically in patients who had previously undergone chemotherapy, in April 2012.
Clinical Data Supporting Pazopanib in RCC
The initial approval of pazopanib was supported by data from a phase 3, multicenter, double-blind trial (NCT00387764) involving 435 patients with locally advanced and/or metastatic RCC. Participants were randomized in a 2:1 ratio to receive either pazopanib at 800 mg once daily (n = 290) or a placebo (n = 145).
The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including overall survival (OS), overall response rate (ORR), and duration of response (DOR).
The intent-to-treat (ITT) analysis revealed a median PFS of 9.2 months in the pazopanib arm compared to 4.2 months in the placebo arm (HR, 0.46; 95% CI, 0.34-0.62). Among treatment-naïve patients, the median PFS was 11.1 months versus 2.8 months, respectively (HR, 0.40; 95% CI, 0.27-0.60). In patients who had received one prior line of cytokine-based systemic therapy, the median PFS was 7.4 months and 4.2 months in the pazopanib and placebo arms, respectively (HR, 0.54; 95% CI, 0.35-0.84).
Pazopanib demonstrated an ORR of 30% (95% CI, 25.1%-35.6%) compared to 3% (95% CI, 0.5%-6.4%) in the placebo group. The median DOR was 58.7 months (95% CI, 52.1-68.1) in the pazopanib arm, while it was not evaluable in the placebo arm.
Final OS analysis showed a median OS of 22.9 months with pazopanib versus 20.5 months with placebo (HR, 0.91; 95% CI, 0.71-1.16). It was also noted that 30% of patients in the pazopanib arm received at least one subsequent line of systemic therapy after disease progression, compared to 66% in the placebo arm.
In terms of safety, 42% and 36% of patients receiving pazopanib experienced dose interruptions and dose reductions, respectively. Common adverse events (AEs) of any grade in RCC patients treated with pazopanib included diarrhea (52%), hypertension (40%), hair color changes (38%), and nausea (26%).
Clinical Data Supporting Pazopanib in Sarcoma
The efficacy of pazopanib in metastatic STS, following prior chemotherapy, was evaluated in the phase 3 VEG110727 trial (NCT00753688). Patients were randomized 2:1 to receive either pazopanib at 800 mg once daily (n = 246) or placebo (n = 123).
The primary endpoint was PFS, assessed via independent radiological review. Secondary endpoints included OS, ORR, and DOR.
The median PFS in the ITT population was 4.6 months with pazopanib versus 1.6 months with placebo (HR, 0.35; 95% CI, 0.26-0.48). Pazopanib treatment also reduced the risk of progression or death compared to placebo in subgroups of patients with leiomyosarcoma (HR, 0.37; 95% CI, 0.23-0.60), synovial sarcoma (HR, 0.43; 95% CI, 0.19-0.98), and other soft tissue sarcomas (HR, 0.39; 95% CI, 0.25-0.60).
The ORR was 4% (95% CI, 2.3%-7.9%) with pazopanib compared to 0% (95% CI, 0.0%-3.0%) with placebo. The median DOR in the pazopanib arm was 9.0 months (95% CI, 3.9-9.2). Final OS analysis showed a median OS of 12.6 months with pazopanib and 10.7 months with placebo (HR, 0.87; 95% CI, 0.67-1.12).
Dose interruptions and reductions were required in 58% and 38% of patients in the pazopanib arm, respectively. The most common AEs of any grade with pazopanib included fatigue (65%), diarrhea (59%), nausea (56%), and decreased weight (48%).
The new pazopanib tablet formulation is anticipated to be launched in the fourth quarter of 2025.