The Phase 3 TiNivo-2 trial, presented at the 2024 European Society for Medical Oncology Annual Congress, investigated the efficacy of rechallenging metastatic renal cell carcinoma (RCC) with an immune checkpoint inhibitor (ICI). The study compared tivozanib plus nivolumab to tivozanib alone in patients who had previously progressed on ICI therapy. The results indicated that adding nivolumab to tivozanib did not improve clinical outcomes in this patient population.
The trial enrolled patients with advanced RCC who had experienced disease progression after one or two prior therapies, including an ICI. Patients were randomized to receive either tivozanib in combination with nivolumab or tivozanib monotherapy. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and response rate as secondary endpoints.
Key Findings
The TiNivo-2 trial demonstrated that the combination of tivozanib and nivolumab did not significantly improve PFS, OS, or response rate compared to tivozanib alone. According to Dr. Toni K. Choueiri, Director of the Lack Center for Genitourinary Oncology at Dana-Farber Cancer Institute, the study results were "dead negative." This outcome aligns with findings from a previous study that showed no benefit from adding atezolizumab to a TKI as an ICI rechallenge.
Implications for Clinical Practice
The results of the TiNivo-2 trial, combined with prior research, suggest that rechallenging with an ICI in metastatic RCC may not be beneficial for most patients who have previously progressed on such therapy. Dr. Choueiri noted that ICI rechallenge should be discouraged outside specific situations, such as a long duration from prior ICI treatment. It's important to note that the dose of tivozanib in the combination arm was lower due to concerns about increased risk of grade 3/4 hypertension, which may have influenced the study's outcomes.
Study Limitations
One limitation of the TiNivo-2 trial is the reduced dose of tivozanib in the combination arm, which was implemented to mitigate the risk of hypertension. This dose reduction could have potentially impacted the efficacy of the combination therapy. Additionally, the study excluded patients with a long duration from prior ICI therapy, limiting the generalizability of the findings to this specific subgroup.
