Real-world outcomes and immune-related adverse events with PD-1/ PD-L1 inhibitors in metastatic renal cell carcinoma: A prospective observational study

Objectives: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have changed the management of metastatic renal cell carcinoma (mRCC). Most pivotal trials come from high-income settings and include highly selected patients. Prospective real-world data from low- and middle- income countries (LMICs), especially from public hospitals in India, are scarce. Material and Methods: This was a single-center, prospective, observational study of adults with histologically confirmed mRCC treated with PD-1/ PD-L1-based regimens at a government cancer center. Eligible patients were ≥18 years, had measurable metastatic disease, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–3. Treatment with nivolumab or pembrolizumab, with or without vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), and line of therapy were chosen by the treating oncologist. Radiological response was assessed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; toxicities were graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with a focus on immune-related adverse events (irAEs). The primary endpoint was objective response rate (ORR) at 3 months; secondary endpoints included toxicity profile and descriptive 12-month outcomes. Results: Thirty-one patients were enrolled. Most had clear-cell histology and intermediate- or poor-risk disease by IMDC criteria. ECOG PS was 0–1 in 19 patients (61%), 2 in 8 (26%), and 3 in 4 (13%). Nineteen patients (61.3%) received PD-1-based therapy as first line, 10 (32.3%) as second line, and 2 (6.5%) as third line. Nivolumab was used in 27 patients (87.1%), mostly as monotherapy; 4 patients (12.9%) received pembrolizumab, including 3 in combination with TKIs (cabozantinib, lenvatinib, or axitinib). At 3 months, 2 patients achieved complete response (CR) and 14 partial responses (PR), yielding an ORR of 51.6%. Only 1 patient had definite progressive disease (PD) at first assessment; the remainder had stable disease or were not fully evaluable. The most common were asthenia (19.4%) and fatigue (12.9%). Immune-related adverse events (AEs) included subclinical hypothyroidism (12.9%), colitis (12.9%), and pneumonitis (9.7%). Treatment discontinuation due to toxicity occurred in 2 patients (severe colitis and pneumonitis). No treatment-related deaths were recorded. Conclusion: In this prospective real-world cohort from an Indian government cancer center—enriched for intermediate- and poor-risk disease and ECOG PS ≥2—PD-1/PD-L1-based therapy produced ORR comparable to pivotal trials, with a manageable toxicity profile. These findings support the feasibility of ICIs in the public-sector LMIC setting and highlight the need for larger multicenter registries to refine patient selection, toxicity management, and access strategies.