Reduced-Dose Pazopanib as First-Line Therapy in Metastatic Renal Cell Carcinoma: Real-World Outcomes and Subsequent...

Immune checkpoint inhibitor-based combinations are the current standard first-line treatment for metastatic renal cell carcinoma (mRCC). However, tyrosine kinase inhibitors remain the predominant first-line therapy in many low- and middle-income countries because of limited affordability and access to immunotherapy. Dose reduction of tyrosine kinase inhibitors is frequently practiced in real-world settings to improve tolerability and treatment adherence. However, data on outcomes with reduced-dose pazopanib and subsequent treatment patterns remain limited. This retrospective study evaluated the effectiveness and safety of reduced-dose pazopanib (400 mg daily) as first-line systemic therapy in anti-VEGF treatment-naive patients with mRCC who were unable to access immunotherapy. Patients aged ≥18 years with histologically confirmed RCC who received reduced-dose pazopanib between January 2016 and December 2023 were included. Data on response rates, toxicities, and subsequent treatment lines were collected from hospital records. Survival outcomes were estimated using the Kaplan-Meier method. Eighty-four patients received reduced-dose pazopanib during the study period. The median age was 57.5 years (range, 19-76 years). Most patients were male (79%) and had clear-cell histology (79.7%). Sixty-six per cent of patients presented with de novo metastatic disease, while 52% belonged to the International Metastatic RCC Database Consortium (IMDC) intermediate-risk group. Nearly half of the cohort (45.1%) had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Nephrectomy was performed in 52 patients (61.9%); of these, radical nephrectomy in 29 (58%) and cytoreductive nephrectomy in 23 (42%). Clinical benefit at the first response assessment was observed in 69 patients (82.1%). At a median follow-up of 41.3 months, median progression-free survival and overall survival were 8.9 months (95% CI, 6.7-11.0 months) and 28.6 months (95% CI, 19.0-38.1 months), respectively. The most common adverse events were skin and hair depigmentation (35.7%), diarrhea (25%), hand-foot syndrome (21.4%), and hypertension (14.3%). Grade 3-4 adverse events occurred in 5.9% of patients, and treatment discontinuation due to toxicity occurred in 2.4%. No treatment-related deaths were reported. Reduced-dose pazopanib appears to be a feasible first-line treatment option for anti-VEGF treatment-naïve patients with mRCC who are unable to access immunotherapy, providing clinically meaningful efficacy with a favorable toxicity profile.