Survival, Efficacy, and Safety Outcomes Beyond Frontline Therapies in mccRCC

Frontline (1L) therapeutic options for metastatic clear cell renal cell carcinoma (mccRCC) are frequently changing, and second-line (2L) treatment decisions are challenging due to limited data comparing 1L and 2L therapies. Researchers compared the survival, efficacy, and safety features of 2L treatment regimens for mccRCC based on the most recent drug approvals and shared the results at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Researchers abstracted overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAEs) hazard ratios, odds ratios, and 95% CI of the treatment differences. P values were used to rank treatments, and data were analyzed in a fixed effects model using the netmeta package in R v.1.5-0. The inclusion criteria for the network meta-analysis (NMA) included phase 2/3 randomized controlled trials that evaluated 2L and beyond for mccRCC.

Nine studies were evaluated, and 10 therapies were included (lenvatinib/everolimus, cabozantinib, lenvatinib alone, axitinib, nivolumab, tivozanib, everolimus, temsirolimus, sorafenib, and pazopanib). Each therapy demonstrated a level of efficacy over placebo treatment.

Pairwise comparisons using the NMA matrix revealed no differential OS benefit between axitinib, cabozantinib, lenvatinib/everolimus, and nivolumab. Other regimens had no OS benefit when compared with placebo.

Lenvatinib/everolimus was found to have the lowest safety profile, but it had the best OS and efficacy based on PFS/ORR. Cabozantinib and nivolumab both showed significant improvement in OS and efficacy over placebo, with lower rates of SAEs compared with lenvatinib/everolimus. Further direct comparison studies are needed to inform clinical practice.